Search

A new polychiral bisabolane sesquiterpene, bisabolanoic acid A (1), was isolated from the mangrove-derived fungus Colletotrichum sp. SCSIO KcB3-2. Its planar structure was identified on the basis o...

Seven unusual new ene-yne hydroquinones (1-3, 5-8), including three rare glycosylated derivatives named pestalotioquinosides A-C (6-8), were obtained from the marine-derived strain SCSIO41403 of the fungus Pestalotiopsis neglecta. Their structures including absolute configurations were elucidated by spectroscopic analysis and induced electronic circular dichroism experiments. In silico molecular docking and in vitro surface plasmon resonance studies showed that pestalotioquinoside C (8) could act as a liver X receptor alpha (LXRα) modulator. Further study showed that LXR target gene ABCA1 was significantly upregulated by 8, which revealed 8 as a potential LXRα agonist.

Twelve indole alkaloids, including α-cyclopiazonic acid (CPA) (1), nine 2-oxo indole CPA derivatives (2–10), and two open-ring indole CPA derivatives (11 and 12), were isolated from the fermentatio...

Background: Due the rarity of occult breast cancer (OBC), no precise prognostic instruments were available to assess the overall survival (OS) in patients with OBC. The aim of this study is to construct a nomogram for predicting the OS probability in patients with OBC. Methods: Patients who were enrolled in the Surveillance, Epidemiology, and End Results database between 2004 and 2015 were regarded as subjects and studied. We constructed a dynamic nomogram that can predict prognosis in patients with OBC based on crucial independent factors by using univariate and multivariate Cox regression analyses. C-index and calibration plots were chosen for validation. Net reclassification index (NRI), integrated discrimination improvement (IDI) and DCA (Ddecision Curve Analysis) were used to evaluate the nomogram’s clinical pragmatism. Results: Totally, 693 patients with OBC were included in this study. The nomogram integrated six independent prognostic factors through multivariate Cox regression analysis, such as surgical method, radiotherapy status, chemotherapy status, ER status, AJCC-stage and age. The prediction model exhibited robustness with the C-index 0.75 (95%CI: 0.72-0.77) in training cohort and 0.79 (95%CI: 0.76-0.82) in validation group. Moreover, the calibration curves presented favorably. The NRI values of 0.61 (95%CI: 0.28-0.99) for 5-year,0.53 (95%CI: 0.23-0.77) for 8-year OS prediction in the training cohort,0.75 (95%CI: 0.36-1.23) for 5-year and 0.6 (95%CI: 0.15-1.2) for 8-year OS prediction in the validation cohort,and the IDI values of 0.1 (95%CI: 0.04-0.17) for 5-year and 0.11 (95%CI: 0.03-0.19) for 8-year OS prediction in the training cohort, 0.21 (95%CI: 0.09-0.3) for 5-year and 0.22 (95%CI: 0.08-0.32) for 8-year OS prediction in the validation cohort,, indicated that the established nomogram performed significantly better than the AJCC stage system alone. Furthermore, DCA showed that the nomogram in our study was clinically useful and had better discriminative ability than the AJCC stage system. Conclusions: A nomogram was developed and validated to accurately predict the individualized probability OS for patients with occult breast cancer (OBC) and is expected to offer guidance for strategic decision.

Background Radiotherapy after breast-conserving surgery (BCS) is not always necessary in older women staged T1N0M0 with low-risk invasive breast cancer, but few studies have concluded the detailed tumor size as a reference for avoiding radiotherapy. The study was conducted to explore and identify the optimal cutoff tumor size. Methods The study population was from the Surveillance, Epidemiology, and End Results (SEER) database in 2010–2016. Propensity score matching was used to balance the confounders between groups. Predictors associated with survival were analyzed by Kaplan–Meier, X-tile, Cox proportional hazards model and competing risk model. Results A total of 52049 women and 3846 deaths were included in the cohort with a median follow-up of 34 months. Based on the cutoff value determined by X-tile analysis, the study population were divided into small tumor group (≤14 mm in diameter) and large tumor group (>14 mm in diameter). Small tumors and radiotherapy were correlated with better breast cancer-specific survival (BCSS). In subgroup analysis, the absolute benefit of BCSS in 6 years attributed to radiotherapy was only 0.90% (RT vs. non- RT:98.77% vs. 97.87%) for patients with small tumors but up to 3.33% (RT vs. non- RT:97.10% vs. 93.77%) for those with large tumors. Conclusion Small tumors and adjuvant radiotherapy were associated with improved long-term prognosis, and 14 mm in diameter was the cutoff tumor size of omitting radiotherapy for patients aged 65 or older with T1N0M0 stage, ER+ and HER2-breast carcinoma after BCS., Graphical abstract Image 1, Highlights • Breast tumor size of 14 mm was the optimal cutoff predicting OS and BCSS. • Small tumors (≤14 mm) and radiotherapy were associated with improved OS and BCSS. • The benefit of radiotherapy was significant in patients with large tumors (>14 mm). • Radiotherapy could be omitted in elders with small low-risk breast tumor after BCS.

Reported as two antirenal cell carcinoma (RCC) drug candidates, marine-derived compounds piericidin A (PA) and glucopiericidin A (GPA) exhibit hepatotoxicity in renal carcinoma xenograft mice. Proteomics and transcriptomics reveal the hepatotoxicity related with cholesterol disposition since RCC is characterized by cholesterol accumulation. PA/GPA aggravate hepatotoxicity in high-cholesterol diet (HCD)-fed mice while exhibiting no toxicity in chow diet-fed mice. High cholesterol accumulation in liver is liver X receptor (LXR)-mediated cytochrome P450 family 7 subfamily a member 1 (CYP7A1) depression and low-density lipoprotein receptor (LDLR) activation. The farnesoid X nuclear receptor (FXR) is also depressed with a downregulated target gene OSTα. Different from PA directly combined with LXRα as an inhibitor, GPA exists as a prodrug in the liver and exerts toxic effects due to transformation into PA. Surface plasmon resonance (SPR) and docking results of 17 piericidins illustrate that glycosides exert no LXRα binding activity. A longer survival time of GPA-treated mice indicates that further exploration in anti-RCC drug research should focus on reducing glycosides transformed into PA and concentrating in the kidney tumor rather than the liver for lowering the risk of hepatotoxicity.

Cache-type phase-change random-access memory is a remaining challenge on the path to universal memory. The recently designed Sc0.2Sb2Te3 (SST) alloy is one of the most promising phase-change materi...

Iakyricidins A-D (1-4), a carbonyl-containing piericidin derivative and three novel piericidin analogues bearing cyclic skeletons, were isolated from the mangrove sediment derived strain Streptomyces iakyrus SCSIO NS104. These structures were established by spectroscopic techniques, Mosher's method, and ECD calculations. Compounds 2-4 represent a novel skeleton of piericidins with branched chain C-C cyclization, and their biosynthetic pathways are proposed. Compound 1, the first natural carbonyl-containing piericidin derivate, exhibited potent antiproliferative activity against ACHN with an IC50 value of 20 nM.

Anti-renal cell carcinoma (RCC) agents with new mechanisms of action are urgently needed. Twenty-seven natural products of the piericidin class, including 17 new ones, are obtained from a marine-derived Streptomyces strain, and several of them show strong inhibitory activities against ACHN renal carcinoma cells. By exploring the mechanisms of two representative natural piericidin compounds, piericidin A (PA) and glucopiericidin A (GPA), peroxiredoxin 1 (PRDX1) is detected as a potential target by transcriptome data of PA-treated ACHN cells, as well as the paired RCC tumor versus adjacent nontumor tissues. PA and GPA induce cell apoptosis through reducing the reactive oxygen species level caused by upregulated PRDX1 mRNA and protein level subsequently and exhibit potent antitumor efficacy in nude mice bearing ACHN xenografts, with increasing PRDX1 expression in tumor. The interaction between PA/GPA and PRDX1 was supported by the docking analysis and surface plasmon resonance. Moreover, the translocation of PRDX1 into the nucleus forced by PA/GPA is proposed to be a key factor for the anti-RCC procedure. Piericidins provide a novel scaffold for further development of potent anti-RCC agents, and the new action mechanism of these agents targeting PRDX1 may improve upon the limitations of existing targeted drugs for the treatment of renal cancer.

One new sesquiterpenoid, 1-methoxypestabacillin B (1), along with one known sesquiterpenoid (2) and six known chrodrimanin-type meroterpenoids (3‒8) were obtained from the solid cultures of a mangrove endophytic fungus Diaporthe sp. SCSIO 41011. Their structures including the absolute configuration at C-6 of compound 1, were determined by extensive spectroscopic analyses and ECD calculations. Meanwhile, the X-ray crystal structures and absolute configurations of two previously reported chrodrimanins E (3) and H (6), are described for the first time. All the compounds were examined for HIV latency-reversal and anti-influenza A virus activities.

A pair of novel lipopeptide epimers, sinulariapeptides A (1) and B (2), and a new phthalide glycerol ether (3) were isolated from the marine algal-associated fungus Cochliobolus lunatus SCSIO41401, together with three known chromanone derivates (4&ndash, 6). The structures of the new compounds, including the absolute configurations, were determined by comprehensive spectroscopic methods, experimental and calculated electronic circular dichroism (ECD), and Mo2 (OAc)4-induced ECD methods. The new compounds 1&ndash, 3 showed moderate inhibitory activity against acetylcholinesterase (AChE), with IC50 values of 1.3&ndash, 2.5 &mu, M, and an in silico molecular docking study was also performed.

BACKGROUND: Cancer will become the leading cause of death worldwide in the 21st century, meanwhile, immunotherapy is the most popular cancer treatment method in recent years. COPI Coat Complex Subunit Beta 1 (COPB1) relates to human innate immunity. However, the role of COPB1 in pan-cancer remains unclear. OBJECTIVE: The purpose of this study was to explore the relationship between COPB1 mRNA expression and tumor infiltrating lymphocytes and immune examination sites in pan-cancer. METHODS: Data from multiple online databases were collected. The BioGPS, UALCAN Database, COSMIC, cBioPortal, Cancer Regulome tools, Kaplan-Meier Plotter and TIMER website were utilized to perform the analysis. RESULTS: Upregulation of COPB1 has been widely observed in tumor tissues compared with normal tissues. Although COPB1 has poor prognosis in pan-cancer, COPB1 high expression was beneficial to the survival of ESCA patients. Unlike ESCA, COPB1 expression in STAD was positively correlated with tumor infiltrating lymphocytes, including B cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. Finally, we also found that the expression of COPB1 in STAD was positively correlated with PD-L1 and CTLA4. CONCLUSIONS: COPB1 may be a prognostic biomarker for pan-carcinoma, and also provide an immune anti-tumor strategy for STAD based on the expression of COPB1.

Background Radiotherapy (RT) after breast-conserving therapy (BCT) is not always necessary in older women staged T1N0M0 with low-risk invasive breast cancer, but few studies have concluded the detailed tumor size as a reference for avoiding RT. We aimed to explore and identify the cutoff tumor size for patients aged 65 or older with T1N0M0 stage and estrogen receptor positive (ER+), human epidermal growth factor receptor 2 positive (HER2-) breast cancer after BCT. Methods The study population was from the Surveillance, Epidemiology, and End Results (SEER) database in 2010 to 2016. Prognostic predictors associated with surgery were used by Kaplan–Meier analysis, X-tile analysis, competing risk model, Fine and Gray multivariable regression model, and propensity score matching (PSM) analysis. Results A total of 52049 women and 3846 deaths were included in the unmatched cohort, of which 11.93% (459/3846) were breast cancer-specific death (BCSD), and 88.07% (3387/3846) were other cause-specific death (OCSD), with a median follow-up of 34 months. Based on the cutoff value of 14 mm determined by X-tile analysis, the study population were divided into small tumor group (tumor ≤ 14 mm in diameter) and large tumor group (tumor ≥ 15 mm in diameter). Subjects in small tumor group and large tumor with RT (large tumor & RT) subgroup tended to have significantly lower cumulative BCSD (Gray’s test, P P P P

The mangrove forests are a complex ecosystem, and the microbial communities in mangrove sediments play a critical role in the biogeochemical cycles of mangrove ecosystems. Mangrove sediments-derived microbes (MSM), as a rich reservoir of natural product diversity, could be utilized in the exploration of new antibiotics or drugs. To understand the structural diversity and bioactivities of the metabolites of MSM, this review for the first time provides a comprehensive overview of 519 natural products isolated from MSM with their bioactivities, up to 2021. Most of the structural types of these compounds are alkaloids, lactones, xanthones, quinones, terpenoids, and steroids. Among them, 210 compounds are obtained from bacteria, most of which are from Streptomyces, while 309 compounds are from fungus, especially genus Aspergillus and Penicillium. The pharmacological mechanisms of some representative lead compounds are well studied, revealing that they have important medicinal potentials, such as piericidins with anti-renal cell cancer effects, azalomycins with anti-MRSA activities, and ophiobolins as antineoplastic agents. The biosynthetic pathways of representative natural products from MSM have also been summarized, especially ikarugamycin, piericidins, divergolides, and azalomycins. In addition, the total synthetic strategies of representative secondary metabolites from MSM are also reviewed, such as piericidin A and borrelidin. This review provides an important reference for the research status of natural products isolated from MSM and the lead compounds worthy of further development, and reveals that MSM have important medicinal values and are worthy of further development.

Three new eremophilane sesquiterpenes, dendryphiellins H-J (1-3), and three new phthalide natural products (4-6) were isolated from the marine-derived fungus Cochliobolus lunatus SCSIO41401. Their structures including absolute configurations were determined by spectroscopic and calculated ECD analyses. Dendryphiellin I (2) showed cytotoxic and antibacterial activities against five cancer cell lines (IC50 1.4 to 4.3 μM) and three bacterial species (MIC 1.5 to 13 μg/mL), respectively. Dendryphiellin J (3), a rare naturally occurring aldoxime analogue, displayed cytotoxicities against ACHN and HepG-2 cells with IC50 values of 3.1 and 5.9 μM, respectively. Further studies indicated that 3 induced apoptosis in ACHN cells in a dose- and time-dependent manner.

Mechanochemical durability is a key limited factor for superhydrophobic coatings to produce the real applications in some important fields. Herein, the superhydrophobic PU-based coatings were firstly synthesized with silica particles (F-SiO2) and carbon nanotube (F-CNT) as the main fillers and the reinforced mediums, respectively. The superhydrophobic coatings showed excellent water repellency with higher water contact angle of 154.3° and lower sliding angle of only 5°. Also, the impacting droplets could rapidly bounced off the superhydrophobic coatings with the contact time of 11 ms. The superhydrophobic coatings exhibited the excellent self-cleaning property. Furthermore, the as-prepared superhydrophobic coatings (F-CNT to F-SiO2 mass ratio was 3:3) possessed the robust mechanochemical durability with higher bonding strength to the aluminum substrates, and the coatings could retain their high superhydrophobicity after over 100 cycles of sand abrasion under a load condition of 1.1 kPa. In strongly acidic and alkaline solutions for 6 h, the composite coatings were intact and showed high ability to resist the chemical erosion. Even though the superhydrophobic coatings suffered the UV damage, the water repellency could be restored under thermal treatment at 135 °C for 3 h. All these excellent performances were attributed to the rational regulation of nanoparticles in superhydrophobic PU-based composite coatings.

Two new α-methoxy- γ-pyrone analogs, 2-methoxy-3-methyl-5,6-diethyl- γ-pyrone (2) and 2-methoxy-3,5-dimethyl-6-propyl- γ-pyrone (3), together with 2-methoxy-3,5-dimethyl-6-ethyl- γ-pyrone (1), firstly isolated from natural sources, were obtained from the EtOAc-solube extract of the mangrove sediment-derived actinomycete strain Streptomyces psammoticus SCSIO NS126, under the optimized fermentation conditions. Their structures were elucidated by detailed spectroscopic analysis and by comparison of their spectroscopic data with those reported in the literature. Those α-methoxy-γ-pyrones were evaluated for their acetylcholinesterase inhibitory activity; however, none of them exhibited obvious activity. Moreover, their biosynthetic relationship with piericidins was also discussed.

Two novel sorbicillinoid adducts containing bicyclo[2.2.2]octane and tetrahydrofuran moieties, named sorbicillfurans A and B (1 and 2), were isolated from the static culture of the marine-derived fungus Penicillium citrinum SCSIO41402. Their structures including absolute configurations were determined by spectroscopic and calculated ECD analyses. Sorbicillfurans A and B (1 and 2) are the first examples of sorbicillinoids possessing a tetrahydrofuran unit. In the proposed biosynthetic pathway, sorbicillfuran B (2), harboring a rare and complex polycyclic framework, is probably formed by two Diels-Alder reactions. Both isolates were evaluated for the cytotoxicity against six human cancer cell lines, only sorbicillfuran B (2) showed weak cytotoxicity against HL-60 cells with an IC50 value of 9.6 μM.

Iakyricidins A-D (

Herein, we designed and fabricated a superhydrophobic fluorinated silica (F-SiO2) @ Polydimethylsiloxane (PDMS) coatings with the great corrosion resistance via a two-step spraying strategy. The superhydrophobic F-SiO2@PDMS coatings displayed higher non-wettability with contact angle of 153.2° and sliding angle only being 3°, when the content of F-SiO2 nanoparticles was 0.88 wt%. The microstructures could entrap more air pockets to form an air-layer at the apparent solid-liquid interface. As a consequence, the F-SiO2@PDMS coatings exhibited the great ability to resist the corrosion effect, where the anti-corrosive mechanisms (or behaviors) were discussed through the two aspects of experimental investigations and molecular modeling. Electrochemical experimental results confirmed that the superhydrophobic F-SiO2@PDMS coatings possessed the excellent corrosion resistance with the corrosion potential Ecorr positively moving to −0.13 V and the corrosion current Icorr as low as 2.0 × 10−7 A cm−2. Also, the electrochemical impedance modulus reached the value of 1.8 × 105 Ω cm−2 and increased approximately 3 orders of magnitude comparing with the aluminum substrate. This was mainly due to the non-wetting regime caused by the trapped air pockets, which was also verified by the electrochemical equivalent circuit. Furthermore, the molecular dynamics simulation accurately revealed the diffusion mechanism of the corrosive medium to further support the discussion of anti-corrosive behavior of superhydrophobic coatings.

Recognizing human gymnastics action is essential to analysis in recent years, the FPGA based recognition is implemented to predict gymnastic action for the different training process accurately. To make such long-term gymnastics training monitoring systems sustainable, it needs smart environments in which the human gymnastics action are recognized automatically. Artificial Neural Network (ANN) based Field-Programmable Gate Array (FPGA) is implemented in this proposed system. Data collected from a smart environment can be used for its machine learning methods to infer human behavior, but these methods need to be trained on annotated datasets. Data sets it records and annotations, are expensive because they require time and human effort. Also, the complexity of human gymnastics allows them to simulate those that are accurately predict the result with help of ANN. Hierarchical models can represent relief more accurately, but finding the right complexity level is not an easy task. Finally, to deploy an automated human action recognition system worldwide, it need model behavior for each new class, with fine-tuning that accurately reflects the behavior of the inhabitants of a particular class. Instead, annotating a dataset that contains weeks of data, the algorithm is most useful for minimizing the need for annotations and maximizing the use of action recognition.

Phase-change random-access memory (PCRAM) is the leading candidate to overcome the intrinsic bottleneck in current von Neumann architecture by unifying computing with storage, enabling its prospect as cognitive memory. However, strong resistance drift in current Ge2Sb2Te5-based PCRAM devices obstructs the accomplishment of high-accuracy computing tasks that require stable multi-state programming. Moreover, the implementation of synaptic depression still remains highly challenging for current PCRAM devices due to the abrupt amorphization nature. We employed 4 nm-thick monatomic antimony (Sb) film to achieve reliable iterative RESET and cumulative SET operations simultaneously, with considerably lowered resistance drift and programming noise. The 2D Sb-based device is also capable of performing progressive RESET operations. Our work thus demonstrates the potential of monatomic 2D PCRAM for the future development of high-performance neuromorphic computing chips.

A new spirocyclic γ-lactam, named spirostaphylotrichin X (1), and three related known spirostaphylotrichins (2-4) were isolated from the marine-derived fungus Cochliobolus lunatus SCSIO41401. Their structures were determined by spectroscopic analyses. Spirostaphylotrichin X (1) displayed obvious inhibitory activities against multiple influenza virus strains, with IC50 values from 1.2 to 5.5 μM. Investigation of the mechanism showed that 1 inhibited viral polymerase activity and interfered with the production of progeny viral RNA. Homogeneous time-resolved fluorescence, surface plasmon resonance assays, and a molecular docking study revealed that 1 could inhibit polymerase PB2 protein activity by binding to the highly conserved region of the cap-binding domain of PB2. These results suggest that 1 inhibits the replication of influenza A virus by interfering with the activity of PB2 protein and that 1 represents a new type of potential lead compound for the development of anti-influenza therapeutics.

Marine micro-organisms in the deep-sea hydrothermal vent systems are considered as potential sources of bioactive natural products. Sixteen bacterial strains were isolated from a deep-sea hydrothermal field and screened for bioactive metabolism studies. After the strains were subjected to bioactive testing at different culture media, chemical dereplication by HPLC coupled to high-resolution mass spectrometer was performed to analyse or determine the main secondary metabolisms in those strains. Strain 06204 was large-scale fermented with relative optimal media, for isolating the desired sulphur compound. Butyrolactone I 3-sulphate was isolated and structurally identified from the extract, guided by dereplication and showed moderate antivirus activities against H3N2 and EV71 viruses. Our study suggests that deep-sea hydrothermal bacteria are good sources of sulphur natural products. Meanwhile, the described approach, mainly bioactive screening, dereplication and targeted isolation, is effective and efficient to discover interesting bioactive compounds in hydrothermal bacteria.

We demonstrate three-dimensional position and force detection of single gold nanosphere (GNP) and gold nanorod (GNR) particles in optical trap by combining backscattered light detection and dark field imaging. The trapping stiffness of the GNPs and GNRs for all three dimensions is measured. The results show that the spring constants in the propagation direction of the trapping laser are somewhat weaker than in other two directions for GNPs. While for GNRs, the spring constants in the polarization direction of the trapping laser are a little weaker than in other two directions. The effect of trapping laser polarization on the particles yields different spring constants in the transverse plane which is perpendicular to the propagation direction. And this effect is larger on GNRs than GNPs.