Gut microbiota from patients with arteriosclerotic CSVD induces higher IL-17A production in neutrophils via activating RORγt.

The intestinal microbiota shape the host immune system and influence the outcomes of various neurological disorders. Arteriosclerotic cerebral small vessel disease (aCSVD) is highly prevalent among the elderly with its pathological mechanisms yet is incompletely understood. The current study investigated the ecology of gut microbiota in patients with aCSVD, particularly its impact on the host immune system. We reported that the altered composition of gut microbiota was associated with undesirable disease outcomes and exacerbated inflammaging status. When exposed to the fecal bacterial extracts from a patient with aCSVD, human and mouse neutrophils were activated, and capacity of interleukin-17A (IL-17A) production was increased. Mechanistically, RORγt signaling in neutrophils was activated by aCSVD-associated gut bacterial extracts to up-regulate IL-17A production. Our findings revealed a previously unrecognized implication of the gut-immune-brain axis in aCSVD pathophysiology, with therapeutic implications.

Response of the photosynthetic activity and biomass of the phytoplankton community to increasing nutrients during cyanobacterial blooms in Meiliang Bay, Lake Taihu.

Nutrient enrichment facilitates algal outbreaks in eutrophic shallow lakes. To further understand the influence of various inorganic nutrient forms on cyanobacterial blooms, a nitrate (NO3 ), ammonium (NH4 ), and orthophosphate (PO4 ) amendment experiment was conducted in a large shallow lake of China (Lake Taihu) during summer. The results showed that the photosynthetic performance of phytoplankton responded more positively to phosphorus (P) than nitrogen (N), and NH4 addition stimulated higher algal photosynthetic activities in P-enriched waters. Individual inorganic N or PO4 addition significantly activated cyanobacteria and green algae. Meanwhile, the N plus P amendment promoted higher biomass of the planktonic microbial community, and the dual addition of NH4  + PO4 yielded the highest chlorophyll a concentration. NH4 additions provisionally promoted higher green algae than cyanobacteria biomass in the beginning, while cyanobacteria dominated again with increasing NH4 :PO4 ratios. These results revealed that increasing ammonium would enhance the increase in phytoplankton biomass in advance and prolong the duration of algal blooms. Hence, based on the control of P loading, the reduction in external inorganic N focusing on ammonium sources (such as ammonia N fertilizer) at the watershed scale would help to alleviate eutrophication and cyanobacterial blooms over the long term in Lake Taihu. PRACTITIONER POINTS: Ammonium addition stimulated higher algal photosynthetic activities in P-enriched waters. Individual inorganic N or PO4 addition significantly activated cyanobacteria and green algae. The dual addition of NH4  + PO4 yielded the highest chlorophyll a concentration. Increasing NH4 would enhance the increase in phytoplankton biomass in advance and prolong the duration of cyanobacterial blooms.

Peptides and polyketides isolated from the marine sponge-derived fungus Aspergillus terreus SCSIO 41008.

Two new isomeric modified tripeptides, aspergillamides C and D (compounds 1 and 2), together with fifteen known compounds (compounds 3-17), were obtained from the marine sponge-derived fungus Aspergillus terreus SCSIO 41008. The structures of the new compounds, including absolute configurations, were determined by extensive analyses of spectroscopic data (NMR, MS, UV, and IR) and comparisons between the calculated and experimental electronic circular dichroism (ECD) spectra. Butyrolactone I (compound 11) exhibited strong inhibitory effects against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with the IC50 being 5.11 ± 0.53 µmol·L-1, and acted as a noncompetitive inhibitor based on kinetic analysis.

Docking- and pharmacophore-based virtual screening for the identification of novel Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) inhibitor with a thiobarbiturate scaffold.

Mycobacterium tuberculosis (Mtb) protein tyrosine phosphatase B (MptpB) is an important virulence factor for Mtb that contributes to survival of the bacteria in macrophages. The absence of a human ortholog makes MptpB an attractive target for new therapeutics to treat tuberculosis. MptpB inhibitors could be an effective treatment to overcome emerging TB drug resistance. Adopting a structure-based virtual screening strategy, we successfully identified thiobarbiturate-based drug-like MptpB inhibitor 15 with an IC50 of 22.4 µM, and as a non-competitive inhibitor with a Ki of 24.7 µM. Importantly, not only did it exhibit moderate cell membrane permeability, compound 15 also displayed potent inhibition of intracellular TB growth in the macrophage, making it an excellent lead compound for anti-TB drug discovery. To the best of our knowledge, this novel thiobarbiturate is the first class of MptpB inhibitor reported so far that leveraged docking- and pharmacophore-based virtual screening approaches. The results of preliminary structure-activity relationship demonstrated that compound 15 identified herein was not a singleton and may inspire the design of novel selective and drug-like MptpB inhibitors.

A New Terminal Cyano Group-containing Benzodiazepine Alkaloid from the Mangrove Endophytic Fungus Penicillium sp. .

A new benzodiazepine alkaloid containing terminal cyano group has been isolated from a mangrove endophytic fungus, Penicillium 299#. Structure elucidation was determined by 1D and 2D NMR spectroscopy and the absolute configuration was determined by electronic circular dichroism (ECD). The new compound showed no cytotoxic activities in vitro against human cancer lines MDA-MB-435, HepG2, HCT-116, and Calu-3.

Polyketides with α-Glucosidase Inhibitory Activity from a Mangrove Endophytic Fungus, Penicillium sp. HN29-3B1.

Five new compounds, pinazaphilones A and B (1, 2), two phenolic compounds (4, 5), and penicidone D (6), together with the known Sch 1385568 (3), (±)-penifupyrone (7), 3-O-methylfunicone (8), 5-methylbenzene-1,3-diol (9), and 2,4-dihydroxy-6-methylbenzoic acid (10) were obtained from the culture of the endophytic fungus Penicillium sp. HN29-3B1, which was isolated from a fresh branch of the mangrove plant Cerbera manghas collected from the South China Sea. Their structures were determined by analysis of 1D and 2D NMR and mass spectroscopic data. Structures of compounds 4 and 7 were further confirmed by a single-crystal X-ray diffraction experiment using Cu Kα radiation. The absolute configurations of compounds 1-3 were assigned by quantum chemical calculations of the electronic circular dichroic spectra. Compounds 2, 3, 5, and 7 inhibited α-glucosidase with IC50 values of 28.0, 16.6, 2.2, and 14.4 µM, respectively, and are thus more potent than the positive control, acarbose.

Vermistatin derivatives with α-glucosidase inhibitory activity from the mangrove endophytic fungus Penicillium sp. HN29-3B1.

Three new vermistatin derivatives, 6-demethylpenisimplicissin (1), 5'-hydroxypenisimplicissin (2), and 2''-epihydroxydihydrovermistatin (3), along with five known vermistatin analogues, methoxyvermistatin (4), vermistatin (5), 6-demethylvermistatin (6), hydroxyvermistatin (7), and penisimplicissin (8), were isolated from the culture of the mangrove endophytic fungus Penicillium sp. HN29-3B1 from Cerbera manghas. Their structures were elucidated mainly by nuclear magnetic resonance spectroscopy. The absolute configurations of compounds 1 and 2 were deduced on the basis of circular dichroism data. The absolute structures of compounds 3 and 5 were confirmed by a single-crystal X-ray diffraction experiment using Cu Kα radiation. In the bioactivity assay, compounds 1 and 3 exhibited α-glucosidase inhibitory activity with IC50 values of 9.5 ± 1.2 and 8.0 ± 1.5 µM, respectively. The plausible biosynthetic pathways for all compounds are discussed.

Meroterpenes and azaphilones from marine mangrove endophytic fungus Penicillium 303#.

Three new metabolites (compounds 1-2 and 6), one azaphilone, and two meroterpenes, together with eleven known compounds have been isolated from a mangrove endophytic fungus, Penicillium 303#. Structure elucidation was achieved by 1D and 2D NMR spectroscopy. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD). Cytotoxic activities of new compounds 1-2 and 6 and compound 7were evaluated in vitro against human cancer lines MDA-MB-435, HepG2, HCT-116, and A549. Those compounds showed weak to moderate cytotoxic activities.

Screening for novel quorum-sensing inhibitors to interfere with the formation of Pseudomonas aeruginosa biofilm.

The objective of this study was to screen for novel quorum-sensing inhibitors (QSIs) from traditional Chinese medicines (TCMs) that inhibit bacterial biofilm formation. Six of 46 active components found in TCMs were identified as putative QSIs based on molecular docking studies. Of these, three compounds inhibited biofilm formation by Pseudomonas aeruginosa and Stenotrophomonas maltophilia at a concentration of 200 µM. A fourth compound (emodin) significantly inhibited biofilm formation at 20 µM and induced proteolysis of the quorum-sensing signal receptor TraR in Escherichia coli at a concentration of 3-30 mM. Emodin also increased the activity of ampicillin against P. aeruginosa. Therefore, emodin might be suitable for development into an antivirulence and antibacterial agent.

Three dimeric naphtho-γ-pyrones from the mangrove endophytic fungus Aspergillus tubingensis isolated from Pongamia pinnata.

Three new dimeric naphtho-γ-pyrones, named rubasperone A (1), rubasperone B (2), and rubasperone C (3), together with two known compounds, rubrofusarin (4) and rubrofusarin B (5), were isolated from the mangrove endophytic fungus Aspergillus tubingensis (GX1-5E). Their structures were determined by spectroscopic methods, including IR, MS, and 1D and 2D NMR. The structures of 1 and 2 were further confirmed by X-ray crystallography. In the bioactivity assays against tyrosinase and α-glucosidase, rubrofusarin (4) exhibited moderate tyrosinase inhibitory activity, with an IC(50) value of 65.6 µM, and rubasperone C (3) showed mild α-glucosidase inhibitory activity, with an IC(50) value of 97.3 µM.

[Analysis of saponin in Chinese ginsengs by NIR spectroscopy].

In the present paper the saponin in Chinese ginseng was analysed quantitatively by using near infrared spectroscopy. The spectral characteristics of the primary ingredients in Chinese ginseng were obtained by applying second derivative, MSC (Multiple Scatter Correction), and correlation chart to the original absorbance spectra of ginseng. Meantime, in combination with the PLS algorithm the calibration process was performed for the quantitative analysis of saponin in Chinese ginseng. The result obtained shows a fine precision of the method, with RMSEC of 0.154% and correlation coefficient of 0.9828.

[Near infrared determination of the total sugar in Chinese ginsengs].

In the present paper the analysis of the total content of sugar in Chinese ginseng was carried out by using near infrared spectroscopy, and in combination with the PLS algorithm the calibration analysis was performed at the same time. The result shows that the precision obtained through common chemical methods is almost the same as the one through NIR spectroscopy. The SEC (standard error of calibration) is 1.9% and the correlation coefficient is 0.951 7, which proves that this technique is well suitable for rapid quantitative determination of the total content of sugar in Chinese ginseng, and is simple, cheap, and without any chemical pollution, and can present real time result.

[Near infrared determination of the content of caffeine in tea polyphenol].

In the present paper the caffeine in the tea polyphenol was analysed spectrally and quantitatively by using near infrared spectroscopy. From the original absorbance of caffeine in the tea polyphenol an obvious and strong peak can be viewed. By using second derivative, MSC (multiple scatter correction) and correlation analysis the spectral characteristics of caffeine in the near infrared region can be seen very clearly, thus the robust calibration model can be set up easily. The result obtained shows that through this technique the absorptive characteristic of those primary fundamentals of caffeine can be looked through easily, meanwhile, calibration test was performed to quantitatively measure the weight percent of caffeine in the tea polyphenol, and fine precision of the result was obtained in a comparatively very large range of concentration. The SEC(standard error of calibration) is 0.49%, and the correlation coefficient r is 0.993. The result shows that NIR is feasible and superior in analyzing the content of caffeine in tea polyphenol.