The fungal diversity in deep-sea environments has recently gained an increasing amount attention. Our knowledge and understanding of the true fungal diversity and the role it plays in deep-sea ...environments, however, is still limited. We investigated the fungal community structure in five sediments from a depth of ∼ 4000 m in the East India Ocean using a combination of targeted environmental sequencing and traditional cultivation. This approach resulted in the recovery of a total of 45 fungal operational taxonomic units (OTUs) and 20 culturable fungal phylotypes. This finding indicates that there is a great amount of fungal diversity in the deep-sea sediments collected in the East Indian Ocean. Three fungal OTUs and one culturable phylotype demonstrated high divergence (89%-97%) from the existing sequences in the GenBank. Moreover, 44.4% fungal OTUs and 30% culturable fungal phylotypes are new reports for deep-sea sediments. These results suggest that the deep-sea sediments from the East India Ocean can serve as habitats for new fungal communities compared with other deep-sea environments. In addition, different fungal community could be detected when using targeted environmental sequencing compared with traditional cultivation in this study, which suggests that a combination of targeted environmental sequencing or traditional cultivation alone. This study is the first to report new insights into the fungal communities in deep-sea sediments environmental sequencing and traditional cultivation will generate a more diverse fungal community in deep-sea environments than using either from the East Indian Ocean, which increases our knowledge and understanding of the fungal diversity in deep-sea environments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A new linear peptide simplicilliumtide I (1) and four new cyclic peptides simplicilliumtides J–M (2–5) together with known analogues verlamelins A and B (6 and 7) were isolated from the ...deep-sea-derived fungal strain Simplicillium obclavatum EIODSF 020. Their structures were elucidated by spectroscopic analysis, and their absolute configurations were further confirmed by chemical structural modification, Marfey’s and Mosher’s methods. Compounds 2, 6, and 7 showed significant antifungal activity toward Aspergillus versicolor and Curvularia australiensis and also had obvious antiviral activity toward HSV-1 with IC50 values of 14.0, 16.7, and 15.6 μM, respectively. The structure–bioactivity relationship of this type of cyclic peptide was also discussed. This is the first time to discuss the effects of the lactone linkage and the substituent group of the fatty acid chain fragment on the bioactivity of this type of cyclic peptides. This is also the first time to report the antiviral activity of these cyclic peptides.
IMPORTANCE: Patients with metastatic colorectal cancer (CRC) have limited effective and tolerable treatment options. OBJECTIVE: To evaluate the efficacy and safety of oral fruquintinib, a vascular ...endothelial growth factor receptor (VEGFR) inhibitor, as third-line or later therapy in patients with metastatic CRC. DESIGN, SETTING, AND PARTICIPANTS: FRESCO (Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients) was a randomized, double-blind, placebo-controlled, multicenter (28 hospitals in China), phase 3 clinical trial. From December 2014 to May 2016, screening took place among 519 patients aged 18 to 75 years who had metastatic CRC that progressed after at least 2 lines of chemotherapy but had not received VEGFR inhibitor therapy; 416 met the eligibility criteria and were stratified by prior anti-VEGF therapy and K-ras status. The final date of follow-up was January 17, 2017. INTERVENTIONS: Patients were randomized in a 2:1 ratio to receive either fruquintinib, 5 mg (n = 278) or placebo (n = 138) orally, once daily for 21 days, followed by 7 days off in 28-day cycles, until disease progression, intolerable toxicity, or study withdrawal. MAIN OUTCOMES AND MEASURES: The primary end point was overall survival. Key secondary efficacy endpoints were progression-free survival (time from randomization to disease progression or death), objectiveresponse rate (confirmed complete or partial response), and disease control rate (complete or partial response, or stabledisease recorded ≥8 weeks postrandomization). Duration of response was also assessed. Safety outcomes included treatment-emergent adverse events. RESULTS: Of the 416 randomized patients (mean age, 54.6 years; 161 38.7% women), 404 (97.1%) completed the trial. Median overall survival was significantly prolonged with fruquintinib compared with placebo (9.3 months 95% CI, 8.2-10.5 vs 6.6 months 95% CI, 5.9-8.1); hazard ratio (HR) for death, 0.65 (95% CI, 0.51-0.83; P < .001). Median progression-free survival was also significantly increased with fruquintinib (3.7 months 95% CI, 3.7-4.6 vs 1.8 months 95% CI, 1.8-1.8 months); HR for progression or death, 0.26 (95% CI, 0.21 to 0.34; P < .001). Grades 3 and 4 treatment-emergent adverse events occurred in 61.2% (170) of patients who received fruquintinib and 19.7% (27) who received placebo. Serious adverse events were reported by 15.5% (43) of patients in the fruquintinib group and 5.8% (8) in the placebo group, with 14.4% (40) of fruquintinib-treated and 5.1% (7) of placebo-treated patients requiring hospitalization. CONCLUSIONS AND RELEVANCE: Among Chinese patients with metastatic CRC who had tumor progression following at least 2 prior chemotherapy regimens, oral fruquintinib compared with placebo resulted in a statistically significant increase in overall survival. Further research is needed to assess efficacy outside of China. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02314819
Patients with metastatic gastric cancer (mGC) who do not respond to or who experience progression with second-line chemotherapy have no treatment options that clearly confer a survival benefit. This ...trial investigated the safety and efficacy of apatinib, an inhibitor of vascular endothelial growth factor receptor, as a treatment option for heavily pretreated patients with mGC.
Patients who experienced treatment failure with at least two chemotherapeutic regimens were randomly assigned to receive placebo (group A), apatinib 850 mg once daily (group B), or apatinib 425 mg twice daily (group C).
We enrolled 144 patients onto this study. In groups A, B, and C, the median overall survival (OS) times were 2.50 months (95% CI, 1.87 to 3.70 months), 4.83 months (95% CI, 4.03 to 5.97 months), and 4.27 months (95% CI, 3.83 to 4.77 months), respectively, and the median progression-free survival (PFS) times were 1.40 months (95% CI, 1.20 to 1.83 months), 3.67 months (95% CI, 2.17 to 6.80 months), and 3.20 months (95% CI, 2.37 to 4.53 months), respectively. There were statistically significant differences between the apatinib and placebo groups for both PFS (P < .001) and OS (P < .001 and P = .0017). Nine patients had a partial response (three patients in group B and six patients in group C). Toxicities were tolerable or could be clinically managed. The most common grade 3 to 4 adverse events were hand-foot syndrome and hypertension. Hematologic toxicities were moderate, and grade 3 to 4 hematologic toxicities were rare.
Apatinib showed improved PFS and OS in heavily pretreated patients with mGC who had experienced treatment failure with two or more chemotherapy regimens.
Four previously undescribed highly oxygenated diterpenoids (
-
), zeylleucapenoids A-D, characterized by halimane and labdane skeletons, were isolated from the aerial parts of
. Their structures were ...elucidated primarily via NMR experiments. The absolute configuration of
was established using theoretical ECD calculations and X-ray crystallographic analysis, whereas those for
-
were assigned using theoretical ORD calculations. Zeylleucapenoids A-D were tested for anti-inflammatory activity against nitric oxide (NO) production in RAW264.7 macrophages, of which only
showed significant efficacy with an IC
value of 38.45 μM. Further, active compound
was also evaluated for the inhibition of the release of pro-inflammatory cytokines TNF-
and IL-6 and was found to have a dose-dependent inhibitory effect, while it showed nontoxic activity for zebrafish embryos. A subsequent Western blotting experiment revealed that
inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, molecular docking analysis indicated that the possible mechanism of action for
may be bind to targets via hydrogen and hydrophobic bond interactions.
Four new xanthene derivatives, penicixanthenes A-D (
-
), and one known compound
were isolated from a marine mangrove endophytic fungus
sp. JY246 that was obtained from the stem of
. Their structures ...were determined by detailed NMR, MS spectroscopic data, modified Mosher's method, and calculated electronic circular dichroism data. All of the isolated compounds were examined for insecticidal activity. Compounds
and
showed growth inhibition activity against newly hatched larvae of
Hubner with the IC
values 100 and 200 μg/mL, respectively, and compounds
,
, and
showed insecticidal activity against newly hatched larvae of
with LC
values of 38.5 (±1.16), 11.6 (±0.58), and 20.5 (±1) μg/mL, respectively. The four xanthene derivatives have the potential to be developed as new biopesticides.
Several ansamycins have been reported to inhibit bacterial biofilm formation and accelerate the eradication of developed biofilms, but little is known about the effect of hygrocin C, an ansamycin, on ...bacterial biofilm formation. Here, hygrocin C was isolated from the marine-derived
Streptomyces
sp. SCSGAA 0027 and reported for the first time to be capable of inhibiting the biofilm formation of
Staphylococcus aureus
and
Bacillus amyloliquefaciens
SCSGAB0082 with the production of anti-microbial lipopeptides from South China Sea gorgonian
Subergorgia suberosa
at concentrations of less than minimum inhibitory concentrations. Moreover, hygrocin C also promoted the eradication of developed biofilms, affected the biofilm architecture, and lowered the extracellular polymeric matrix formation, cell motility, and surface hydrophobicity in
B
.
amyloliquefaciens
, which was in accordance with the inhibition of biofilm formation. Furthermore, transcriptome analysis revealed that hygrocin C altered the transcripts of several genes associated with bacterial chemotaxis and flagellar, two-component system and the synthesis of arginine and histidine, which are important for bacterial biofilm formation. In conclusion, hygrocin C could be used as a potential biofilm inhibitor against
S
.
aureus
and
B
.
amyloliquefaciens
. But further genetic investigations are needed to provide more details for elucidation of the molecular mechanisms responsible for the effects of hygrocin C on
B
.
amyloliquefaciens
biofilm formation.
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•Four new peptides 1–4 were isolated from Aspergillus sp. SCSIO 41501.•Their structures were elucidated by spectroscopic analysis and Marfey’s method.•Compounds 1 and 2 showed evident ...antiviral activity against HSV-1.
A new cyclic pentapeptide and three new linear peptides, namely, aspergillipeptides D–G (1–4), were isolated from a culture broth of marine gorgonian-derived fungus Aspergillus sp. SCSIO 41501. Their structures were elucidated by spectroscopic analysis, and their absolute configurations were confirmed by Marfey’s method. Compounds 1 and 2 showed evident antiviral activity against herpes simplex virus type 1 (HSV-1) with IC50 values of 9.5 and 19.8µM under their non-cytotoxic concentrations against a Vero cell line, respectively, and 1 also had antiviral activity against acyclovir-resistant clinical isolates of HSV-1.
Recently, the activation of persulfate (PDS) by non-metallic photocatalysts under visible light has attracted significant interest in applications in environmental remediation. This study presents a ...pioneering investigation into the combined application of the TpTt-COF and PMS for visible light degradation of organic dyes. Synthesized orange TpTt-COF monomers exhibit exceptional crystallinity, a 2D structure, and notable stability in harsh conditions. The broad visible light absorption around a wavelength of 708 nm. The TpTt-COF emerges as a promising candidate for photocatalytic dye degradation. The study addresses high charge recombination in the TpTt-COF, highlighting the crucial role of its electron donor and acceptor for the PMS activation. Comparative analyses against traditional photocatalytic materials, such as the metal-free carbon-based material g-C
N
and transition metal-containing TiO
, demonstrate TpTt-COF's superior performance, generating diverse free radicals. In simulated experiments, the TpTt-COF's degradation rate surpasses PMS-combined g-C
N
by 13.9 times. and 1.6 times higher than the TpTt-COF alone. Remarkably, the TpTt-COF maintains high activity under harsh environments. Investigations into the degradation mechanism and the TpTt-COF's reusability reveal its efficiency and stability. Under visible light, TpTt-COF facilitates efficient electron-hole separation. Combining the TpTt-COF with PMS produces various radicals, ensuring effective separation and a synergistic effect. Radical quenching experiments confirm the pivotal role of O
· radicals, while ·OH and SO
· radicals intensify the degradation. After five cycles, TpTt-COF maintains an impressive 83.2% degradation efficiency. This study introduces an efficient photocatalytic system mediated by PMS and valuable insights into governing mechanisms for organic pollutant degradation in water environments.
Three new lactones penicilactones A-C (
-
) were obtained from the mangrove-derived fungus
sp. TGM112. Their structures and absolute configurations were determined by detailed NMR, MS spectroscopic ...data, Mo
(OAc)
-induced electronic circular dichroism (ECD), and circular dichroism (CD) spectroscopy. Compound
showed antibacterial activity against
with an MIC value of 6.25 μg/mL. Compound
showed insecticidal activity against newly hatched larvae of
with the LC
value of 78.5 (±0.58) μg/mL.
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