Azaphilone pigments from the marine-derived Penicillium sclerotium UJNMF 0503 and their neuroprotective potential against H2O2-induced cell apoptosis through modulating PI3K/Akt pathway.

Azaphilones represent a particular group of fascinating pigments from fungal source, with easier industrialization and lower cost than the traditional plant-derived pigments, and they also display a wide range of pharmacological activities. Herein, 28 azaphilone analogs, including 12 new ones, were obtained from the fermentation culture of a marine fungus Penicillium sclerotium UJNMF 0503. Their structures were elucidated by MS, NMR and ECD analyses, together with NMR and ECD calculations and biogenetic considerations. Among them, compounds 1 and 2 feature an unusual natural benzo[d][1,3]dioxepine ring embedded with an orthoformate unit, while 3 and 4 represent the first azaphilone examples incorporating a novel rearranged 5/6 bicyclic core and a tetrahydropyran ring on the side chain, respectively. Our bioassays revealed that half of the isolates exhibited neuroprotective potential against H2O2-induced injury on RSC96 cells, while compound 13 displayed the best rescuing capacity toward the cell viability by blocking cellular apoptosis, which was likely achieved by upregulating the PI3K/Akt signaling pathway.

Anisotropic medium sensing controlled by bound states in the continuum in polarization-independent metasurfaces.

Bound states in the continuum (BICs) with infinite quality factor (Q-factor) and significant field enhancement pave the way for realizing highly sensitive optical sensors with enhanced light-matter interactions on the nanoscale. However, current optical sensing methods are difficult to discriminate between isotropic and anisotropic media from resonance spectral lines, resulting in optical sensing methods still being limited to isotropic media. In this work, we demonstrate that BICs can be realized by modulating the period of structural units to convert BICs to QBICs without changing their space group symmetry, and propose a polarization-independent metasurfaces-based realization of highly sensitive refractive index sensors for isotropic and anisotropic media as well as discrimination. We propose a metasurface of tetrameric silicon nanoboxes with C4 symmetry as structural units to achieve the conversion of BICs to QBICs by modulating the period of structural units without changing the geometry of the structure. Two QBICs modes dominated by electric toroidal dipole and magnetic toroidal dipole are identified by multipolar decomposition and electromagnetic distribution calculations. Meanwhile, we realize the refractive index detection and resolution of isotropic and anisotropic media based on polarization-independent metasurfaces combined with isotropic and anisotropic media layers. Our work provides what we believe to be a new method for realizing the fast resolution and refractive index optical sensing of isotropic and anisotropic media, and offers new ideas for the design and application of polarization-independent metasurfaces.

Indole Diterpenes from Mangrove Sediment-Derived Fungus Penicillium sp. UJNMF0740 Protect PC12 Cells against 6-OHDA-Induced Neurotoxicity via Regulating the PI3K/Akt Pathway.

In our chemical investigation into Penicillium sp. UJNMF0740 derived from mangrove sediment, fourteen indole diterpene analogs, including four new ones, are purified by multiple chromatographic separation methods, with their structures being elucidated by the analyses of NMR, HR-ESIMS, and ECD data. The antibacterial and neuroprotective effects of these isolates were examined, and only compounds 6 and 9 exhibited weak antibacterial activity, while compounds 5, 8, and 10 showed protective effects against the injury of PC12 cells induced by 6-hydroxydopamine (6-OHDA). Additionally, compound 5 could suppress the apoptosis and production of reactive oxygen species (ROS) in 6-OHDA-stimulated PC12 cells as well as trigger the phosphorylation of PI3K and Akt. Taken together, our work enriches the structural diversity of indole diterpenes and hints that compounds of this skeleton can repress the 6-OHDA-induced apoptosis of PC12 cells via regulating the PI3K/Akt signaling pathway, which provides evidence for the future utilization of this fascinating class of molecules as potential neuroprotective agents.

Tunable liquid crystal core refractive index sensor based on surface plasmon resonance in gold nanofilm coated photonic crystal fiber.

We propose, to the best of our knowledge, a novel kind of tunable liquid crystal core refractive index (RI) sensor based on photonic crystal fiber (PCF) covered with a nanoring gold film. The finite element method is used to discuss and analyze the sensing performance of the RI sensor. Gold is used as the excitation material for surface plasmon resonance, and a gold nanoring is embedded around the first cladding of the PCF. The liquid analytes penetrate the outermost layer of the cladding, and the central hole is filled with liquid crystal E7. Complete coupling and incomplete coupling are excited as the analyte RI increases, and the resonance strength of complete coupling is stronger than that of incomplete coupling. It can be proved by calculation that at different wavelengths, resonant coupling of fifth-order and sixth-order surface plasmon polaritons is obtained. The RI of liquid analytes ranges from 1.405 to 1.445. The diameters of the liquid crystal cores are 0.2, 0.4, 0.6, and 0.8 µm; their average sensitivities are 10700, 10566, 10167, and 9166 nm/RIU; and the linear fitting constants are 0.98025, 0.97387, 0.96597, and 0.95507, respectively. In short, the RI sensor has the advantages of tunability, wide range, and high sensitivity, and is expected to be applied in various fields.

Double U-groove temperature and refractive index photonic crystal fiber sensor based on surface plasmon resonance.

Based on double U-groove photonic crystal fiber (PCF), a surface plasmon resonance sensor with dual parametric detection of temperature and refractive index is proposed. The birefringence of PCF is increased by using germanium ions doped in the core and introducing U-shaped notches on both sides of the D-shaped fiber. The polished surface of the PCF is coated with gold film and PDMS as a temperature sensing channel, and the U-shaped groove is coated with gold film as a refractive index sensing channel. Through the design of the sensor, it is finally possible to achieve independent measurement of the two parameters. The sensor has a maximum wavelength sensitivity of 4715 nm/RIU in the analyte refractive index range of 1.32-1.4, and maximum wavelength sensitivity of 18 nm/°C in the ambient temperature range of -30∘C-50∘C. The proposed sensor has broad application prospects in scenarios such as blood analysis, DNA hybridization analysis, and microenvironmental cell interactions.

Effect of different reinforcement methods on anastomotic leakage prevention after laparoscopic double anastomosis.

BACKGROUND AND OBJECTIVES: To investigate the effects of different suture reinforcement methods for anastomotic leakage and other postoperative complications after the use of a laparoscopic double stapling technique (DST). METHODS: We collected the data of 124 patients who underwent laparoscopic radical resection of colorectal cancer from July 2017 to September 2018 at our institution. Patients were divided into three groups according to the suture reinforcement methods: intermittent, continuous suture reinforcement, and non-reinforcement (n = 41, 41, and 42, respectively). One-way analysis of variance, χ2 , Fisher's exact, and nonparametric tests were used for statistical analysis. RESULTS: Among the 124 patients, there were no statistically significant differences in operation times, intraoperative blood loss, postoperative hospital stays and recovery of bowel movement. Nine patients were diagnosed with anastomotic leakage (AL). The incidences of serious AL in the intermittent and continuous suture reinforcement groups were lower than that in the control group, with lower reoperation rate, shorter average lengths of stay and lower treatment costs of two experimental groups. CONCLUSION: Intermittent and continuous sutures after laparoscopic DST is effective, safe, and feasible on anastomotic leakage prevention. These procedures could be popularized in rectal surgery on patients with high risk of AL.

Research on tunable distributed SPR sensor based on bimetal film.

In order to overcome the limitations in range of traditional prism structure surface plasmon resonance (SPR) single-point sensor measurement, a symmetric bimetallic film SPR multi-sensor structure is proposed. Based on this, the dual-channel sensing attenuation mechanism of SPR in gold and silver composite film and the improvement of sensing characteristics were studied. By optimizing the characteristics such as material and thickness, a wider range of dual-channel distributed sensing is realized. Using a He-Ne laser (632.8 nm) as the reference light source, prism-excited symmetric SPR sensing was studied theoretically for a symmetrical metal-clad dielectric waveguide using thin-film optics theory. The influence of the angle of incidence of the light source and the thickness of the dielectric layer on the performance of SPR dual formant sensing is explained. The finite-difference time-domain method was used for the simulation calculation for various thicknesses and compositions of the symmetric combined layer, resulting in the choice of silver (30 nm) and gold (10 nm). When the incident angle was 78 deg, the quality factor reached 5960, showing an excellent resonance sensing effect. The sensitivity reached a maximum of 5.25×10-5 RIU when testing the water content of an aqueous solution of honey, which proves the feasibility and practicality of the structure design. The structure improves the theoretical basis for designing an SPR multi-channel distributed sensing system, which can greatly reduce the cost of biochemical detection and significantly increase the detection efficiency.

Meroterpenoids and Isocoumarinoids from a Myrothecium Fungus Associated with Apocynum Venetum.

Four new meroterpenoids 1⁻4 and four new isocoumarinoids 5⁻8, along with five known isocoumarinoids (9⁻13), were isolated from the fungus Myrothecium sp. OUCMDZ-2784 associated with the salt-resistant medicinal plant, Apocynum venetum (Apocynaceae). Their structures were elucidated by means of spectroscopic analysis, X-ray crystallography, ECD spectra and quantum chemical calculations. Compounds 1⁻5, 7, 9 and 10 showed weak α-glucosidase inhibition with the IC50 values of 0.50, 0.66, 0.058, 0.20, 0.32, 0.036, 0.026 and 0.37 mM, respectively.

Marine natural products sourced from marine-derived Penicillium fungi.

Marine micro-organisms have been proven to be a major source of marine natural products (MNPs) in recent years, in which filamentous fungi are a vital source of bioactive natural products for their large metagenomes and more complex genetic backgrounds. This review highlights the 390 new MNPs from marine-derived Penicillium fungi during 1991 to 2014. These new MNPs are categorized based on the environment sources of the fungal hosts and their bioactivities are summarized.

[New natural products from the marine-derived Aspergillus fungi-A review].

Marine-derived fungi were the main source of marine microbial natural products (NPs) due to their complex genetic background, chemodiversity and high yield of NPs. According to our previous survey for marine microbial NPs from 2010 to 2013, Aspergillus fungi have received the most of attention among all the marine-derived fungi, which accounted for 31% NPs of the marine fungal origins. This paper reviewed the sources, chemical structures and bioactivites of all the 512 new marine NPs of Aspergillus fungal origins from 1992 to 2014. These marine NPs have diverse chemical structures including polyketides, fatty acids, sterols and terpenoids, alkaloids, peptides, and so on, 36% of which displayed bioactivities such as cytotoxicity, antimicrobial activity, antioxidant and insecticidal activity. Nitrogen compounds are the major secondary metabolites accounting for 52% NPs from the marine-derived Aspergillus fungi. Nitrogen compounds are also the class with the highest ratio of bioactive compounds, 40% of which are bioactive. Plinabulin, a dehydrodiketopiperazine derivative of halimide had been ended its phase II trial and has received its phase III study from the third quarter of 2015 for the treatment of advanced, metastatic non-small cell lung cancer.

Research on Multiscale Modeling and Experiment of CFRP Milling.

High-quality milling of carbon fiber reinforced polymer (CFRP) composites is of great importance for the high-performance manufacturing of structures made of this hard-to-machine material. In this paper, a multiscale finite element (FE) model, considering the thermal-mechanical coupling effect, was developed to simulate the milling process and reveal its material removal mechanism. The corresponding milling experiments were conducted to validate the simulated cutting forces and temperature, which were in good agreement with the experiment results. In the macroscale model, the Hashin failure criteria were used to estimate the failure of the composites. In the microscale model, the fibers, matrix, and the fiber-matrix interface were modeled separately, to investigate the mechanisms of material removal behavior during milling, among fiber breakage, matrix cracking, and fiber-matrix debonding. Based on the macroscale numerical and experimental results, the higher cutting speed was demonstrated to improve the surface quality of CFRP milling. According to the results from the microscale model, the material removal mechanism varies depending on the orientation of the fibers and can be divided into four stages. The outcome of this work provides guidelines to further investigate optimal manufacturing parameters for the milling of CFRP composites and their cutting mechanisms.

Sharing and Integration of Cognitive Neuroscience Data: Metric and Pattern Matching across Heterogeneous ERP Datasets.

In the present paper, we use data mining methods to address two challenges in the sharing and integration of data from electrophysiological (ERP) studies of human brain function. The first challenge, ERP metric matching, is to identify correspondences among distinct summary features ("metrics") in ERP datasets from different research labs. The second challenge, ERP pattern matching, is to align the ERP patterns or "components" in these datasets. We address both challenges within a unified framework. The utility of this framework is illustrated in a series of experiments using ERP datasets that are designed to simulate heterogeneities from three sources: (a) different groups of subjects with distinct simulated patterns of brain activity, (b) different measurement methods, i.e, alternative spatial and temporal metrics, and (c) different patterns, reflecting the use of alternative pattern analysis techniques. Unlike real ERP data, the simulated data are derived from known source patterns, providing a gold standard for evaluation of the proposed matching methods. Using this approach, we demonstrate that the proposed method outperforms well-known existing methods, because it utilizes cluster-based structure and thus achieves finer-grained representation of the multidimensional (spatial and temporal) attributes of ERP data.

High Birefringence D-Shaped Germanium-Doped Photonic Crystal Fiber Sensor.

In this work, a surface plasmon resonance (SPR) sensor based on a D-shaped germanium-doped photonic crystal fiber (PCF) is proposed. The finite element method (FEM) is introduced to analyze the structure parameters, such as germanium-doped concentration, lattice pitch, and air hole size. In addition, the coupling properties and birefringence properties of PCF are also studied. The computer simulation results indicate that two different surface plasmon polariton (SPP) coupling modes are produced on the polished surface, covered with metal film, when the analyte refractive index (RI) is 1.34. Then, with the increase of the RI, the incompleteness of one of the coupling modes will be transformed into the complete coupling. The effect of germanium concentration on the birefringence is also analyzed. It has an optimal wavelength sensitivity of 5600 nm/RIU when the RI is 1.37. This sensor exhibits a maximum birefringence of 1.06 × 10-2 and a resolution of 1.78 × 10-5 RIU with high linearity.

A Cyclohexapeptide and Its Rare Glycosides from Marine Sponge-Derived Streptomyces sp. OUCMDZ-4539.

Pyridapeptide A (1), a cyclohexapeptide containing hexahydropyridazine-3-carboxylic acid (HPDA), 5-hydroxytetrahydropyridazine-3-carboxylic acid (γ-OH-TPDA), and (2S,3R,4E,6E)-2-amino-3-hydroxy-8-methylnona-4,6-dienoic acid residues, and its four glycopeptides, pyridapeptides B-E (2-5, respectively), were isolated from the fermentation broth of the marine sponge-derived Streptomyces sp. OUCMDZ-4539. Their structures were determined on the basis of spectroscopic analysis and chemical methods. Pyridapeptides B-E have one or more 2,3,6-trideoxyhexose sugar units glycosylated at the γ-OH-TPDA residue. The biosynthetic pathways were proposed on the basis of gene cluster analysis. Compounds 4 and 5, containing four sugar groups, displayed significant antiproliferative activity against five human cancer cell lines (PC9, MKN45, HepG2, HCT-116, and K562).

OMIT: a domain-specific knowledge base for microRNA target prediction.

Identification and characterization of the important roles microRNAs (miRNAs) perform in human cancer is an increasingly active research area. Unfortunately, prediction of miRNA target genes remains a challenging task to cancer researchers. Current processes are time-consuming, error-prone, and subject to biologists' limited prior knowledge. Therefore, we propose a domain-specific knowledge base built upon Ontology for MicroRNA Targets (OMIT) to facilitate knowledge acquisition in miRNA target gene prediction. We describe the ontology design, semantic annotation and data integration, and user-friendly interface and conclude that the OMIT system can assist biologists in unraveling the important roles of miRNAs in human cancer. Thus, it will help clinicians make sound decisions when treating cancer patients.

Detection and Clinical Value of Circulating Tumor Cells as an Assisted Prognostic Marker in Colorectal Cancer Patients.

BACKGROUND: Circulating tumor cells (CTCs) are cells that have been shed into the vasculature from a primary tumor and circulate in the bloodstream. It has been suggested that detecting CTCs could help the clinician to detect early metastasis or recurrence more effectively. This trial sets out to assess the detection and clinical value of CTCs as an assisted prognostic marker in patients with colon cancer and rectal cancer. METHODS: A prospective cohort of patients with colorectal cancer (CRC) was enrolled from July 2015 to February 2018 in Shanghai Minimally Invasive Surgery Center, Shanghai, China. In this study, 149 patients with CRC were enrolled and underwent surgical treatment. There were 79 cases of colon cancer and 70 cases of rectal cancer, including 93 males and 56 females. To investigate the correlativity and clinical value of CTCs, the patients were statistically analyzed in different subgroups: colon cancer group vs rectal cancer group, and left hemicolon cancer group vs right hemicolon cancer group. RESULTS: The results of analysis comparing CTC counts and clinical pathological features in colon and rectal cancer indicated that with increased tumor stage, the number of CTCs also increased, with significant statistical differences. CTC counts in patients with colon and rectal cancer showed positive correlations with TNM staging (P=0.001, 0.013, respectively), T staging (P=0.021, 0.001), N staging (P=0.014, 0.035) and M staging (P=0.018, 0.203). Detection of serum biomarkers in CTC-positive and CTC-negative groups indicated a significantly increasing expression in the CTC-positive group. To confirm the correlations between CTCs and histoembryological differences, analysis was conducted with the patients in two subgroups: left hemicolon cancer group and right hemicolon cancer group. The results showed that the positive rate of CTCs increased in both groups with the increase in tumor stage. The survival analysis indicated that there was a steep gradient in survival in the follow-up period, particularly in the CTC-positive group (P=0.000). Risk assessment curves showed that the change escalated more rapidly in the CTC-positive group. Furthermore, with the increase in T stage, changes in the survival curve and risk curve escalated more rapidly in the CTC-positive group. CONCLUSION: It was confirmed that in the left hemicolon cancer group, a much higher coincidence rate could be found on CTC-positive rate and clinicopathological features, than in the right hemicolon cancer group. The sensitivity of CTCs may be related to the histoembryological location of the tumor, lymphatic metastasis and the depth of infiltration. Monitoring CTCs may have value in evaluating clinical staging and estimating clinical prognosis.

Identification of 1-phenyl-4-cyano-5-aminopyrazoles as novel ecdysone receptor ligands by virtual screening, structural optimization, and biological evaluations.

Ecdysteroids initiate the molting process in insects by binding to the ecdysone receptor (EcR), which is a promising target for identifying insect growth regulators. This paper presents an in silico/in vitro screening procedure for identifying new EcR ligands. The three-step virtual screening procedure uses a three-dimensional pharmacophore model, docking and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) rescoring routine. A novel hit (VS14) with good binding activity against Plutella xylostella EcR was identified from a library of over 200,000 chemicals. Subsequently, the 1-phenyl-4-cyano-5-aminopyrazole scaffold and twelve EcR ligands were synthesized. Their IC50 values against Plutella xylostella EcR ranged from 0.64 to 23.21 µm. Furthermore, a preliminary analysis of the structure-activity relationship for novel scaffolds provided a basis for designing new ligands with improved activity.

Cytotoxic and antibacterial triterpenoids from the roots of Morinda officinalis var. officinalis.

Seven new pentacyclic triterpenoids including six ursane-type, marinoids A-F (1-6), and one oleanane-type, marinoid G (7), along with five known analogues (8-12), were separated from the roots of Morinda officinalis var. officinalis. Their structures were assigned by spectroscopic means especially analysis of 2D NMR data, with the absolute configurations of 1 and 2 being determined via comparison of their experimental ECD spectra with the computed ones. Selective compounds displayed cytotoxic activity against two human osteosarcoma cell lines and also antibacterial effects against one Gram positive and one Gram negative strains.

Cherry extract on post-exercise muscle damage / Extrato de cereja em danos musculares pós-exercício / El extracto de cereza daños musculares post ejercicio

ABSTRACT Introduction: Cherry extract has a high amount of anthocyanins and flavonoids containing antioxidant effects. Its high antioxidant characteristics have been shown to reduce markers of delayed muscle soreness (DOMS) and exercise-induced muscle damage (EIMD) to improve recovery after exercise. Objective: Verify the effects of the cherry extract on post-exercise muscle damage. Methods: Google scholar, Medline, and Scopus were systematically searched until February 2022. The Cochrane Collaboration tool was applied to determine the risks of bias. Results: The results showed that cherry extract administration did not have a decreasing impact on creatine kinase levels overall: (WMD = 12.85 IU. L-1, 95% CI: −35.94, 61.64; P = 0.606). Considerable heterogeneity was observed among the articles (Cochran's Q-test = 990.80, P = 0.000, I2 = 96.7 %). However, there is a significant reducing effect on pain sensation by the consumption of cherry extract (WMD = −6.105 mm; 95% CI: −11.193 −1.017; p = 0.019). Conclusion: Cherry extract consumption effectively reduced late-onset muscle pain among participants in the overall and subgroup analysis. Thus, the cherry extract may be a complementary alternative in recovery after exercise. Level of evidence II; Therapeutic studies - Manuscript review.

RESUMO Introdução: O extrato de cereja tem uma alta quantidade de antocianinas e flavonóides contendo efeitos antioxidantes. Suas altas características antioxidantes demonstraram reduzir os marcadores de dor muscular retardada (DOMS) e dano muscular induzido pelo exercício (EIMD) para melhorar a recuperação após o exercício. Objetivo: Verificar os efeitos do extrato de cereja nos danos musculares pós-exercício. Métodos: Google scholar, Medline e Scopus foram sistematicamente pesquisados até fevereiro de 2022. A ferramenta de colaboração da Cochrane foi aplicada para determinar os riscos de viés. Resultados: Os resultados mostraram que a administração do extrato de cereja não teve um impacto decrescente nos níveis de creatina quinase em geral: (WMD = 12,85 IU. L-1, 95% CI: −35,94, 61,64; P = 0,606). Uma heterogeneidade considerável foi observada entre os artigos (teste Q da Cochran = 990,80, P = 0,000, I2 = 96,7 %). Porém, há um efeito redutor significativo na sensação de dor pelo consumo de extrato de cereja (WMD = −6,105 mm; 95% CI: −11,193 −1,017; p = 0,019). Conclusão: O consumo de extrato de cereja foi efetivo na redução de dores musculares de início tardio entre os participantes, na análise geral e nos subgrupos. Assim, o extrato de cereja pode ser uma alternativa complementar na recuperação após os exercícios. Nível de evidência II; Estudos terapêuticos - Revisão de manuscritos.

RESUMEN Introducción: El extracto de cereza tiene una gran cantidad de antocianinas y flavonoides con efectos antioxidantes. Se ha demostrado que sus altas características antioxidantes reducen los marcadores de dolor muscular retardado (DOMS) y el daño muscular inducido por el ejercicio (EIMD) para mejorar la recuperación después del ejercicio. Objetivo: Verificar los efectos del extracto de cereza en el daño muscular posterior al ejercicio. Métodos: Se realizaron búsquedas sistemáticas en Google scholar, Medline y Scopus hasta febrero de 2022. Se aplicó la herramienta de colaboración Cochrane para determinar los riesgos de sesgo. Resultados: Los resultados mostraron que la administración de extracto de cereza no tuvo un impacto decreciente en los niveles de creatina quinasa en general: (WMD = 12,85 UI. L-1, IC del 95%: −35,94, 61,64; P = 0,606). Se observó una considerable heterogeneidad entre los artículos (prueba Q de Cochran = 990,80, P = 0,000, I2 = 96,7 %). Sin embargo, el consumo de extracto de cereza tiene un efecto significativo de reducción del dolor (WMD = −6,105 mm; IC del 95%: −11,193 −1,017; p = 0,019). Conclusión: El consumo de extracto de cereza fue eficaz para reducir el dolor muscular de aparición tardía entre los participantes en el análisis global y de subgrupos. Así, el extracto de cereza puede ser una alternativa complementaria en la recuperación después de los ejercicios. Nivel de evidencia II; Estudios terapéuticos - Revisión de manuscritos.

Natural Products Research in China From 2015 to 2016.

This review covers the literature published by chemists from China during the 2015-2016 on natural products (NPs), with 1,985 citations referring to 6,944 new compounds isolated from marine or terrestrial microorganisms, plants, and animals. The emphasis is on 730 new compounds with a novel skeleton or/and significant bioactivity, together with their source organism and country of origin.