Terpenoids from the Soft Coral Stereonephthya bellissima.

A detailed chemical study of the extract from the soft coral Stereonephthya bellissima resulted in the isolation and identification of seven new sesquiterpenoids, bellissinanes A-G (1-7), along with four new diterpenes (8-11). Bellissinane A (1) is the third reported nardosinane-type sesquiterpene bearing a 6/5/6 tricyclic system. Bellissinanes C and D (3, 4) contain a phenylethylamine fragment, which is relatively unusual in marine organisms. Bellissinanes E-G (5-7) belong to the rare class of nornardosinane sesquiterpenoids. Structurally uncommon octahydro-1H-indenyl-type and prenyleudesmane-type skeletons were characterized for herpetopanone B (8) and bellissimain A (9), respectively. Bellissinane E (5) exhibited in vivo angiogenesis-promoting activity.

[Content determination of ten flavonoids and alkaloids in Gleditsiae Sinensis Fructus, Gleditsiae Fructus Abnormalis, and Gleditsiae Spina].

To study the quality control of three traditional Chinese medicines derived from Gleditsia sinensis [Gleditsiae Sinensis Fructus(GSF), Gleditsiae Fructus Abnormalis(GFA), and Gleditsiae Spina(GS)], this paper established a multiple reaction monitoring(MRM) approach based on ultra-high performance liquid chromatography-triple quadrupole-linear ion-trap mass spectrometry(UHPLC-Q-Trap-MS). Using an ACQUITY UPLC BEH C_(18) column(2.1 mm × 100 mm, 1.7 µm), gradient elution was performed at 40 ℃ with water containing 0.1% formic acid-acetonitrile as the mobile phase running at 0.3 mL·min~(-1), and the separation and content determination of ten chemical constituents(e.g., saikachinoside A, locustoside A, orientin, taxifolin, vitexin, isoquercitrin, luteolin, quercitrin, quercetin, and apigenin) in GSF, GFA, and GS were enabled within 31 min. The established method could quickly and efficiently determine the content of ten chemical constituents in GSF, GFA, and GS. All constituents showed good linearity(r>0.995), and the average recovery rate was 94.09%-110.9%. The results showed that, the content of two alkaloids in GSF(2.03-834.75 µg·g~(-1)) was higher than that in GFA(0.03-10.41 µg·g~(-1)) and GS(0.04-13.66 µg·g~(-1)), while the content of eight flavonoids in GS(0.54-2.38 mg·g~(-1)) was higher than that in GSF(0.08-0.29 mg·g~(-1)) and GFA(0.15-0.32 mg·g~(-1)). These results provide references for the quality control of G. sinensis-derived TCMs.

USP18 reduces paclitaxol sensitivity of triple-negative breast cancer via autophagy.

Paclitaxol is a first-line treatment for triple-negative breast cancer (TNBC). The molecular mechanisms underlying paclitaxol resistance in TNBC remain largely unclear. In this study, differential expressed genes (DEGs) between TNBC cells and paclitaxol-resistant (taxol-R) TNBC cells were screened by bioinformatics analysis. Among these DEGs, USP18 mRNA expression was significantly increased in taxol-R TNBC cells. USP18 overexpression reduced paclitaxol sensitivity by decreasing paclitaxol-induced apoptosis and cell cycle arrest in TNBC cells. In contrast, USP18 knockdown increased paclitaxol mediated anticancer activity in taxol-R TNBC cells in vitro and in vivo. Mechanistically, USP18 induced autophagy, an important pathway in chemotherapy resistance. The autophagy inhibitor leupeptin could effectively reverse the effect of USP18 on paclitaxol resistance phenotype. These findings suggested that USP18 may be a promising target for overcoming paclitaxol resistance in TNBC.

[Comparative study on anti-depressant effect of Zhizichi Decoction and its solid fermentation product on CUMS rats].

Chronic unpredicted mild stress(CUMS) combined with isolated feeding was used to induce depressed rat model. The anti-depressant effects of Zhizichi Decoction(ZZCD) and its solid fermented product(ZZC) were analyzed by behavioral test and comparison of pathological tissues of hippocampus and liver, metabolic characteristics of intestinal flora, and relative abundance of species. The results showed that ZZC could increase sucrose preference, shorten the immobility time in the forced swim test and tail suspension test(P<0.05), and repair damaged hippocampus and liver tissues, and the effect was superior to that of ZZCD. The results of Biolog ECO plates showed that the average well color development(AWCD) of intestinal flora in the model group significantly decreased and the metabolic levels of sugar and amino acids were reduced, while the AWCD of the treatment groups increased. The metabolic levels of the two carbon sources were improved in the ZZC group, while only sugar metabolic level was elevated in the ZZCD group. Metagenomic analysis of intestinal flora showed that the ratio of Firmicutes/Bacteroidetes was 3.87 in the control group, 21.77 in the model group, 5.91 in the ZZC group, and 18.48 in the ZZCD group. Lactobacillus increased by 3.28 times, and Prevotella and Bacteroidetes decreased by 75.59% and 76.39%, respectively in the model group as compared with that in the control group. Lactobacillus decreased by 31.13%, and Prevotella and Bacteroidetes increased by more than three times in the ZZC group as compared with that in the model group, while the corresponding changes in the ZZCD group were not significant. ZZC could improve depression-like beha-viors by regulating the structure of intestinal flora and metabolic functions and repairing damaged hippocampus and liver tissues in depressed rats, showing an anti-depressant effect superior to that of ZZCD. This study is expected to provide a basis for the development of new anti-depressant food products.

Genetic variation in ZmTIP1 contributes to root hair elongation and drought tolerance in maize.

Drought is a major abiotic stress that threatens maize production globally. A previous genome-wide association study identified a significant association between the natural variation of ZmTIP1 and the drought tolerance of maize seedlings. Here, we report on comprehensive genetic and functional analysis, indicating that ZmTIP1, which encodes a functional S-acyltransferase, plays a positive role in regulating the length of root hairs and the level of drought tolerance in maize. We show that enhancing ZmTIP1 expression in transgenic Arabidopsis and maize increased root hair length, as well as plant tolerance to water deficit. In contrast, ZmTIP1 transposon-insertional mutants displayed the opposite phenotype. A calcium-dependent protein kinase, ZmCPK9, was identified as a substrate protein of ZmTIP1, and ZmTIP1-mediated palmitoylation of two cysteine residues facilitated the ZmCPK9 PM association. The results of this research enrich our knowledge about ZmTIP1-mediated protein S-acylation modifications in relation to the regulation of root hair elongation and drought tolerance. Additionally, the identification of a favourable allele of ZmTIP1 also provides a valuable genetic resource or selection target for the genetic improvement of maize.

Expression and function of phosphodiesterases (PDEs) in the rat urinary bladder.

BACKGROUND: It has been shown that hosphodiesterases (PDEs) play an important role in mediating the smooth muscle tone of rat urinary bladder. However, the gene expression profiles of them were still unknown. METHODS: Urinary bladder Strips were obtained from both neonatal and adult Sprague-Dawley rats. RT-PCR/western blot and organ bath were used to measure the expression and function of PDEs. RESULTS: Adult rat urinary bladder expressed various PDE mRNA with the following rank order: PDE5A ≈ PDE9A ≈ PDE10A > PDE2A ≈ PDE4A ≈ PDE4D > PDE4B ≈ PDE3B ≈ PDE8B ≈ PDE7A ≈ PDE7B > PDE1A. PDE1B, PDE1C, PDE3A, PDE4C, PDE8A, and PDE11A were not detected. Of interest, the mRNA and protein of PDE3A were significantly decreased in adult rat urinary bladder compared to neonatal rat urinary bladder. Cilostamide, a specific inhibitor for PDE3, significantly inhibited the amplitude and frequency of carbachol-enhanced phasic contractions of neonatal rat bladder strips by 38.8% and 12.1%, respectively. Compared to the neonatal rat bladder, the effect of cilostamide was significantly blunted in adult rat urinary bladder: the amplitude and frequency of carbachol-enhanced phasic contractions were decreased by 13.4% (P < 0.01 vs neonatal rat bladder) and 4.4%, respectively. However, the mRNA and the protein levels of PDE3B were similar between neonatal and adult rat bladder. CONCLUSION: We found that several PDE isoforms were expressed in the rat urinary bladder with distinct levels. Moreover, we showed that the function of PDE3 was blunted in adult rat bladder likely due to the decreased expression of PDE3A.

New Peptides Isolated from Marine Cyanobacteria, an Overview over the Past Decade.

Marine cyanobacteria are significant sources of structurally diverse marine natural products with broad biological activities. In the past 10 years, excellent progress has been made in the discovery of marine cyanobacteria-derived peptides with diverse chemical structures. Most of these peptides exhibit strong pharmacological activities, such as neurotoxicity and cytotoxicity. In the present review, we summarized peptides isolated from marine cyanobacteria since 2007.

Laparoscopic versus open partial nephrectomy for multilocular cystic renal cell carcinoma: a direct comparison based on single-center experience.

OBJECTIVES: To compare the treatment of laparoscopic (LPN) versus open partial nephrectomy (OPN) in patients with multilocular cystic renal cell carcinoma (MCRCC). METHODS: Thirty-seven patients diagnosed with MCRCC were reviewed retrospectively between January 2007 and January 2013 at our institution. They were divided into two groups: group 1 (LPN) consisted of 19 patients (51.4%) and group 2 (OPN) of 18 patients (48.6%). RENAL and the Preoperative Aspects and Dimensions Used for an Anatomical classification were applied to predict perioperative complications, which were graded based on the Clavien-Dindo classification. RESULTS: The two groups were comparable with regard to all of the patients' baseline characteristics. In group 1, the mean operative time was 142.1 min, including the mean warm ischemia time (WIT) of 32.6 min; the mean estimated blood loss (EBL) was 96.1 ml, the mean retroperitoneal drainage lasted 3.6 days, and the mean postoperative hospital stay was 5.3 days. In group 2, the figures were 126.6 and 23.5 min, 223.3 ml, and 4.6 and 8.7 days, respectively. The differences in WIT, EBL, drainage days and hospitalization were statistically significant between both groups (p < 0.05). No recurrence or new lesions occurred in these patients during a mean follow-up of 37.8 months. CONCLUSIONS: Our single-center experience suggests that although it remains technically complex, demanding and challenging for MCRCC, LPN can still induce favorable perioperative results and survival rates in MCRCC are comparable with OPN.

Laparoscopic partial nephrectomy for multilocular cystic renal cell carcinoma: a potential gold standard treatment with excellent perioperative outcomes.

BACKGROUND: To report on the perioperative outcomes of laparoscopic partial nephrectomy (LPN) for multilocular cystic renal cell carcinoma (MCRCC) and evaluate the feasibility of this minimally invasive technique as a potential gold standard treatment for MCRCC. METHODS: We retrospectively reviewed the database of surgically pathological findings of patients who were diagnosed with MCRCC at Peking University First Hospital and Chinese PLA General Hospital (Beijing, China) between May 2009 and January 2013. A total of 42 patients with an average age of 48.3 years who were treated with LPN were collected. The patients' perioperative outcomes were reported and analyzed. RESULTS: All operations were performed successfully without massive hemorrhage or open conversion. None of patients received lymph node dissection or metastasectomy. Two patients required postoperative transfusion with a mean amount of 175 cc packed red blood cells. Only three patients experienced mild postoperative complications. The mean operative time was 2.4 ± 1.2 hours, including the mean warm ischemia time (WIT) of 23.2 ± 5.7 minutes. The mean estimated blood loss was 72.0 ± 49.6 ml. The mean retroperitoneal drainage was 4.4 ± 1.7 days. The mean postoperative hospital stay was 6.1 ± 1.9 days. Pathologically, 40 (95.2%) of the tumors presented as stage pT1abN0M0, while the remaining two (4.8%) presented as stage pT2aN0M0. No recurrences or new lesions occurred in these patients at a mean follow-up time of 30.0 months. CONCLUSIONS: Although the effective option of LPN is not yet the gold standard treatment for conventional renal cell carcinoma, it should be strongly recommended as a potential gold standard treatment for MCRCC due to the benign nature of MCRCC and the excellent perioperative outcomes provided by LPN.

Sarcocinerenolides A, an open-loop decarbonizing cembranolide, and sarcocinerenolides B-I, eight polyoxygenated cembranolides with anti-thrombotic activity from the South China Sea soft coral Sarcophyton cinereum.

A previously undescribed open-loop decarbonizing cembranolide, sarcocinerenolide A, and eight undescribed cembranolides, sarcocinerenolides B-I, characterized by poly-membered oxygen ring fragments were isolated from the soft coral Sarcophyton cinereum collected from the South China Sea. The structures and absolute configurations of these previously undescribed compounds were precisely determined by analysis of NMR data, DP4+ and ECD spectra. The bioactivities of the compounds were evaluated using zebrafish models and sarcocinerenolides C and H exhibited anti-thrombotic activity.

Anti-inflammatory and cytotoxicity nitrogenous merosesquiterpenoids from the sponge Pseudoceratina purpurea.

Fourteen undescribed nitrogenous merosesquiterpenoids, purpurols A-D (1-4) and puraminones A-J (5-14), along with three known related compounds (15-17) were isolated from the sponge Pseudoceratina purpurea collected in the South China Sea. Their structures and absolute configurations were unambiguously elucidated by a combination of spectroscopic data, X-ray diffraction analysis, electronic circular dichroism calculations, and chemical derivatization. Purpurols A-D (1-4) incorporated nitrogenous heterocycles, compounds 1 and 2 feature an unusual benzothiazole ring, while 3 and 4 feature benzoxazole ring. Puraminones A-J (5-14) represent sesquiterpenoid aminoquinones with different amine and amino acid side chains at C-20. Additionally, twenty unreported sesquiterpenoid aminoquinone analogues were obtained through chemical derivatization. It is worth noting that all compounds are featured with unusual rearranged 4,9-friedodrimane subunit. In the bioassays, purpurols A and B showed weak anti-inflammation in zebrafish, as well as some compounds showed activities against tumor cells, therefore, preliminary structure-cytotoxicity relationships are also discussed.

Gram-scale solvothermal synthesis of Fe-doped CuCoO2 nanosheets and improvement of the oxygen evolution reaction performance.

In this work, we used Cu-BTC-IPA and Co(NO3)2·6H2O as precursors to synthesize CuCoO2 (CCO) nanocrystals with a suitable crystal phase, morphology and high yield by changing the process parameters, such as reactant concentration, reactant ratio, mineralizer dosage, and the type of polyvinylpyrrolidone surfactant. In addition, the effects of different concentrations (1 at%, 3 at%, 5 at%) of Fe doping on the crystal structure and oxygen evolution reaction (OER) performance of CCO were studied. The experimental results show that Fe ions are uniformly doped into the lattice to replace the A-site (Cu+) position, which not only reduces the grain size of CCO, but also increases its specific surface area. We further employed the density functional theory (DFT) method to simulate the OER process of transition metal Fe-doped CCO (A-site substitution) and proposed that Fe doping can reduce the Gibbs free energy of each step and promote the formation of each intermediate, thereby improving its OER catalytic performance. In 1.0 M KOH electrolyte, the 3 at% Fe-doped CCO (Ni@3FCCO) electrode has the best OER performance (η10 = 369 mV, Tafel slope = 69 mV dec-1), and the required overpotential to attain 10 mA cm-2 slightly increased (∼30.2 mV) after 18 hours of continuous OER. The crystal morphology and chemical composition did not change significantly before and after the long-term OER test, indicating that the 3FCCO nanosheets have good OER activity and stability. We have proposed two reasons for the significant improvement of OER performance for Fe-doped CCO nanosheets: (1) the partial substitution of Cu cations by Fe cations not only regulates the electronic structure of CCO, making the catalytically active center no longer a single Co site, but also contains the Fe site, thus increasing the number of overall active sites; (2) the synergistic effect between Fe cations and Co cations in the OER process could enhance the activity of a single active site.

Recurrent Cystitis Associated With 2 Programmed Death 1 Inhibitors: A Rare Case Report and Literature Review.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancer, however, often with immune-related adverse events (irAEs). Adverse events involving the bladder were extremely rare with only few cases. Herein, we described a rare, recurrent cystitis associated with 2 programmed death 1 inhibitors (pembrolizumab and toripalimab) in 1 patient with advanced liver cancer. Cystitis associated with toripalimab, a novel humanized programmed death 1 monoclonal antibody, was first presented in our case. Cystitis is an extremely rare irAE associated with ICIs, especially anti-programmed death 1 antibodies. With widening indications of ICIs in clinical practice, physicians should be also aware of this rare irAE.

Sarcoelegans A-H, eight undescribed cembranes with anti-inflammatory and anti-thrombotic activities from the South China Sea soft coral Sarcophyton elegans.

Chemical investigation of the South China Sea soft coral Sarcophyton elegans has led to the isolation of eight undescribed cembranes, namely sarcoelegans A-H. Their structures and absolute configurations were unambiguously established by extensive analyses of spectroscopic data, X-ray diffraction, QM-NMR, and TDDFT-ECD calculations. Sarcoelegan A is composed of the rare tricyclo [11.2.1.0] hexadecane carbon framework which is the third compound of this scaffold. Sarcoelegan B and sarcoelegan C possess an unusual seven-membered ether ring, and (±)-sarcoelegan D has a seven-membered ring with the rare peroxo bridge. In addition, sarcoelegan A, (±)-sarcoelegan D, sarcoelegan E, (+)-sarcoelegan F, and (+)-sarcoelegan H exhibited anti-inflammatory activity in zebrafish and sarcoelegan C exhibited anti-thrombotic activity in zebrafish.

Somatic and germline aberrations in homologous recombination repair genes in Chinese prostate cancer patients.

Simple summary: Somatic and germline aberrations in homologous recombinant repair (HHR) genes are associated with increased incidence and poor prognosis for prostate cancer. Through next-generation sequencing of prostate cancer patients across all clinical states from north China, here the authors identified a somatic mutational rate of 3% and a germline mutational rate of 3.9% for HRR genes using 200 tumor tissues and 714 blood specimens. Thus, mutational rates in HRR genes were lower compared with previous studies. Background: Homologous recombination repair deficiency is associated with higher risk and poorer prognosis for prostate cancer. However, the landscapes of somatic and germline mutations in these genes remain poorly defined in Chinese patients, especially for those with localized disease and those from north part of China. In this study, we explore the genomic profiles of these patients. Methods: We performed next-generation sequencing with 200 tumor tissues and 714 blood samples from prostate cancer patients at Peking University First Hospital, using a 32 gene panel including 19 homologous recombination repair genes. Results: TP53, PTEN, KRAS were the most common somatic aberrations; BRCA2, NBN, ATM were the most common germline aberrations. In terms of HRR genes, 3% (6/200) patients harbored somatic aberrations, and 3.8% (28/714) patients harbored germline aberrations. 98.0% (196/200) somatic-tested and 72.7% (519/714) germline tested patients underwent prostatectomy, of which 28.6% and 42.0% had Gleason scores ≥8 respectively. Gleason scores at either biopsy or prostatectomy were predictive for somatic aberrations in general and in TP53; while age of onset <60 years old, PSA at diagnosis, and Gleason scores at biopsy were clinical factors associated with positive germline aberrations in BRCA2/ATM. Conclusions: Our results showed a distinct genomic profile in homologous recombination repair genes for patients with prostate cancer across all clinical states from north China. Clinicians may consider to expand the prostate cancer patients receiving genetic tests to include more individuals due to the weak guiding role by the clinical factors currently available.

Comparative Characterization of the Ginsenosides from Six Panax Herbal Extracts and Their In Vitro Rat Gut Microbial Metabolites by Advanced Liquid Chromatography-Mass Spectrometry Approaches.

Ginseng extracts are extensively used as raw materials for food supplements and herbal medicines. This study aimed to characterize ginsenosides obtained from six Panax plant extracts (Panax ginseng, red ginseng, Panax quinquefolius, Panax notoginseng, Panax japonicus, and Panax japonicus var. major) and compared them with their in vitro metabolic profiles mediated by rat intestinal microbiota. Ultrahigh-performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) with scheduled multiple reaction monitoring (sMRM) quantitation methods were developed to characterize and compare the ginsenoside composition of the different extracts. After in vitro incubation, 248 ginsenosides/metabolites were identified by UHPLC/IM-QTOF-MS in six biotransformed samples. Deglycosylation was determined to be the main metabolic pathway of ginsenosides, and protopanaxadiol-type and oleanolic acid-type saponins were easier to be easily metabolized. Compared with the ginsenosides in plant extracts, those remaining in six biotransformed samples were considerably fewer after biotransformation for 8 h. However, the compositional differences in four subtypes of the ginsenosides among the six Panax plants became more distinct.

Comprehensive Investigation of Genes Associated with Cell Cycle Pathways for Prognosis and Immunotherapy in Bladder Urothelial Carcinoma.

Bladder urothelial carcinoma (BLCA) is estimated to cause approximately 150,000 deaths per year worldwide. The prognosis of BLCA remains dismal, so early detection can have a significant impact on clinical outcomes. Numerous studies have shown that genes can alter the progression of tumors by regulating cell cycle, thus achieving targeted therapy. A comprehensive comparison analysis of expression profiles in BLCA datasets downloaded from Gene Expression Omnibus (GEO) was conducted to identify common differentially expressed genes (DEGs) using R packages. Gene Set Enrichment Analysis (GSEA) of identified DEGs was performed, and a protein-protein interaction (PPI) network was mapped using Cytoscape software. The expression of hub genes was validated in GEPIA2, cBioPortal, and ONCOMINE databases. The potential roles of the cell cycle genes (CCGs) in immunity were also explored. A total of 70 DEGs from GSE13507, GSE37815, and GSE52519 were identified commonly, including 23 up-regulated and 47 down-regulated genes. GSEA and PPI analysis revealed genes in the cell cycle pathway significantly enriched in tumor tissues, and the expression of 12 CCGs was up-regulated. Furthermore, significant differences of the CCGs expression were found in different immune subtypes of BLCA. The expression of CCGs was closely related to CD4+ T cell, memory B cell, eosinophil, monocyte, T helper cell, and many marker genes of immunomodulators. Abundance of tumor-infiltrating lymphocytes were associated with patients' overall survival with BLCA. Increased CCG expression was correlated with better prognosis in BLCA patients, together with higher immune infiltration levels in CD4 T activated memory cell, and CD8 T central cell, respectively. The up-regulated CCGs in BLCA tumor tissues played important roles in immune cell infiltration and could be novel targets for tumor immunotherapy in BLCA.

[Eukaryotic expression of human Y-box binding protein 1 (YB-1) promotes the proliferation and migration of human HepG2 cells].

Objective To establish the eukaryotic expression vector of Y-box-binding protein 1 (YB-1) with FLAG-tagged and transfect it into hepatocellular carcinoma HepG2 cells to identify the effects of YB-1 on the proliferation and migration. Methods Human YB-1 gene was amplified from the human ovary library by PCR. YB-1 fraction was double enzyme digested and connected with pcDNA3.0-FLAG vector to construct eukaryotic expression vector pcDNA3.0-FlAG-YB-1, which was transfected into HepG2 cells. The expression of YB-1 was detected by Western blotting, and the effect of YB-1 on the proliferation of HepG2 cells was determined by CCK-8 assay and clone formation. The effect of YB-1 on the migration of HepG2 cells was analyzed by wound healing assays. Results The eukaryotic expression vector pcDNA3.0-FLAG-YB-1 was successfully established. YB-1 protein can be expressed in HepG2 cells, and YB-1 promoted the proliferation and migration of HepG2 cells. Conclusion YB-1 promotes the proliferation and migration of HepG2 cells.

Interaction between BEND5 and RBPJ suppresses breast cancer growth and metastasis via inhibiting Notch signaling.

High frequent metastasis is the major cause of breast cancer (BC) mortality among women. However, the molecular mechanisms underlying BC metastasis remain largely unknown. Here, we identified six hub BC metastasis driver genes (BEND5, HSD11B1, NEDD9, SAA2, SH2D2A and TNFSF4) through bioinformatics analysis, among which BEND5 is the most significant gene. Low BEND5 expression predicted advanced stage and shorter overall survival in BC patients. Functional experiments showed that BEND5 could suppress BC growth and metastasis in vitro and in vivo. Mechanistically, BEND5 inhibits Notch signaling via directly interacting with transcription factor RBPJ/CSL. BEN domain of BEND5 interacts with the N-terminal domain (NTD) domain of RBPJ, thus preventing mastermind like transcriptional coactivator (MAML) from forming a transcription activation complex with RBPJ. Our study provides a novel insight into regulatory mechanisms underlying Notch signaling and suggests that BEND5 may become a promising target for BC therapy.