A derivative of trihydroxynaphthalenone and a pyrone metabolite from the endophytic fungus Talaromyces purpurpgenus.

A newly discovered trihydroxynaphthalenone derivative, epoxynaphthalenone (1) involving the condensation of ortho-hydroxyl groups into an epoxy structure, and a novel pyrone metabolite characterized as pyroneaceacid (2), were extracted from Talaromyces purpurpgenus, an endophytic fungus residing in Rhododendron molle. The structures of these compounds were elucidated through a comprehensive analysis of their NMR and HRESIMS data. The determination of absolute configurations was accomplished using electronic circular dichroism (ECD) calculations and CD spectra. Notably, these recently identified metabolites exhibited a moderate inhibitory activity against xanthine oxidase (XOD).

The application of high-throughput sequencing technology in corneal diseases.

High-throughput sequencing technology, also known as next-generation sequencing technology, can explore new biomarkers and specific gene mutations. It has a pivotal role in promoting the gene research, which can limit the detection area, lessen the time needed for sequencing. Also, it can quickly screen out the suspected pathogenic genes of patients, gain the necessary genetic data, and provide the basis for clinical diagnosis and genetic counseling. In the research of corneal diseases, through the DNA sequencing of patients' diseased cells, it can provide a deeper understanding of corneal diseases and improve the diagnosis, classification and treatment alternatives of various corneal diseases. This article will introduce the application progress of high-throughput sequencing technology in corneal diseases, which will help to understand the application of this technology in various corneal diseases.

A systematic scoping review of epidemiological studies on the association between organophosphate flame retardants and neurotoxicity.

Organophosphate flame retardants (OPFRs) are increasingly and widely used as substitutes for brominated flame retardants in daily life. The chemical structure of OPFRs is very similar to that of organophosphorus pesticides, leading to concerns about their neurotoxicity. A few epidemiological studies have been published with inconsistent results on this topic, and a systematic scoping review is needed to provide an overview or map of the current evidence on the relationship of OPFRs with neurodevelopmental toxicity. Therefore, MEDLINE (accessed through PubMed), Web of Science, and CNKI (Chinese National Knowledge Infrastructure) were systematically searched for articles published in the last two decades. Nine eligible articles were included in the present systematic scoping review for adherence to the predefined PECOS (population, exposure, comparison, outcome, study design) statement. Six studies were conducted in the USA, and the remaining three studies were conducted in Austria, Norway and China. A total of 2 581 children (1 203 females and 1 378 males) were included. Half of the included studies focused on the adverse effects of OPFR exposure on cognition in children, while others primarily focused on the behaviors of children. In summary, the current evidence suggests inverse associations between early-life exposure to OPFRs and the childhood intelligence quotient and internalizing behavior and positive relationships of OPFR exposure with externalizing behavior. However, some differences in the timing of sample collection for exposure measurements, in the individual OPFR metabolites available, in the neurodevelopmental scales for outcome measurement, and in the statistical methods used to analyze the data are noted. In addition, further studies are warranted to evaluate some important issues, such as sex differences in the association, exposure-sensitive periods, and cumulative exposure risk assessment.

Halomonas bachuensis sp. nov., Isolated from Gobi Soil.

A novel aerobic bacterium designated DX6T was isolated from a Gobi soil sample collected in Bachu County, China. Cells are Gram-stain-negative and rod-shaped and colonies are creamy, circular and smooth. The growth range of NaCl concentration was 1-15% (optimum 2-10%, w/v). Growth occurs at 10-45 °C (optimum 37 °C) and pH 5.0-10.0 (optimum pH 7.0-9.0). Phylogenetic analysis of the 16S rRNA gene sequences indicated that strain DX6T formed a distinct lineage in the clade of genus Halomonas and is related to Halomonas desiderata DSM 9502T (98.3%), Halomonas kenyensis AIR-2T (97.7%), Halomonas daqingensis DQD2-30T (97.6%), Halomonas saliphila LCB169T (97.4%) and Halomonas endophytica MC28T (96.2%). Analysis of the housekeeping genes gryB and rpoD and calculation of the average nucleotide identities and the digital DNA-DNA hybridization values between strain DX6T and the related type Halomonas strains further revealed that strain DX6T represented a distinct species. The main respiratory quinones of strain DX6T were ubiquinone 9 (Q-9) and ubiquinone 8 (Q-8). The predominant cellular fatty acids were summed feature 8 (C18:1ω7c and/or C18:1ω6c), summed feature 3 (C16:1ω7c and/or C16:1ω6c) and C16:0. The major polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids, an unidentified phosphatidylglycolipid, and four unidentified lipids. Based on the phenotypic, phylogenetic, chemotaxonomic and genomic features, strain DX6T represents a novel species of the genus Halomonas. The name Halomonas bachuensis sp. nov. is proposed with strain DX6T (= CCTCC AB 2020094T = KCTC 82196T) designated as the type strain.

Long noncoding RNA SMAD5-AS1 acts as a microRNA-106a-5p sponge to promote epithelial mesenchymal transition in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial cancer of the head and neck with high prevalence in southern China, which is accompanied by notable invasiveness and metastasis. Long noncoding RNAs (lncRNAs) participate in the progression of various cancers including NPC. Microarray-based analysis identified highly expressed lncRNA mothers against decapentaplegic homolog 5 (SMAD5)-antisense RNA 1 (AS1) related to NPC. Interestingly, it is found that SMAD5-AS1 competitively bound to microRNA (miR)-106a-5p to regulate SMAD5. Herein, the study aimed to clarify the role of SMAD5-AS1/miR-106a-5p/SMAD5 axis in the process of epithelial mesenchymal transition (EMT) in NPC. SMAD5-AS1 was highly expressed and miR-106a-5p was poorly expressed in NPC tissues and cell lines. The NPC cells were treated with a series of small interfering RNAs, mimics, or inhibitors to explore the effects of SMAD5-AS1, SMAD5, and miR-106a-5p on EMT, cell proliferation, migration, and invasion in NPC. Of note, SMAD5-AS1 silencing or miR-106a-5p overexpression reduced expression of N-cadherin, matrix metallopeptidase 9, Snail, and Vimentin while elevating E-cadherin expression, thus inhibiting EMT, cell proliferation, migration, and invasion in NPC by down-regulation of SMAD5. Moreover, SMAD5 silencing could reduce the ability of EMT induced by SMAD5-AS1 up-regulation. SMAD5-AS1 silencing or miR-106a-5p elevation inhibited tumorigenesis in nude mice. Taken together, SMAD5-AS1 silencing suppressed EMT, cell proliferation, migration, and invasion in NPC by elevating miR-106a-5p to down-regulate SMAD5, which provided a novel therapeutic target for NPC treatment.-Zheng, Y.-J., Zhao, J.-Y., Liang, T.-S., Wang, P., Wang, J., Yang, D.-K., Liu, Z.-S. Long noncoding RNA SMAD5-AS1 acts as a microRNA-106a-5p sponge to promote epithelial mesenchymal transition in nasopharyngeal carcinoma.

Fungi: outstanding source of novel chemical scaffolds.

A large number of remarkable studies on the secondary metabolites of fungi have been conducted in recent years. This review gives an overview of one hundred and sixty-seven molecules with novel skeletons and their bioactivities that have been reported in seventy-nine articles published from 2013 to 2017. Our statistical data showed that endophytic fungi and marine-derived fungi are the major sources of novel bioactive secondary metabolites.

Tetramethylpyrazine production from edible materials by the probiotic Bacillus coagulans.

2,3,5,6-Tetramethylpyrazine (TMP) has health care functions, especially for cardiovascular and cerebrovascular health. In this study, we found that Bacillus coagulans, a well-known probiotic, has the capability to produce acetoin, a precursor of TMP. The culture conditions and medium for the production of TMP by B. coagulans CICC 20138 were optimized. Then, a novel three-step process was successfully performed for the production of TMP from edible materials by B. coagulans. First, in the acetoin enrichment process, 12.61 ± 0.34 g/L acetoin was generated at 36 h. Second, in the spore enrichment process, various factors were optimized to make the bacteria produce more spores to improve the resistance to subsequent high-temperature reactions. Third, in the TMP enrichment process, the final concentration of TMP and B. coagulans spores contained in the product reached 2.54 ± 0.26 g/L and 8.81 × 108 CFU/mL at 46 h, respectively. This is the first report of using a probiotic bacterium to produce TMP. Using edible materials and the probiotic strain, this work provides a novel method for the production of a TMP food additive rich in B. coagulans spores.

Fermentative production of chiral acetoin by wild-type Bacillus strains.

In recent years, there have been many studies on producing acetoin by microbial fermentation, while only a few studies have focused on chiral acetoin biosynthesis. The weight assignment method was first applied to balance the chiral purity (expressed as the enantiomeric excess value) and the titer of acetoin. Bacillus sp. H-18W, a thermophile, was selected from seven Bacillus strains for chiral acetoin production. To lower the cost of the fermentation medium, soybean meal was used as a feedstock. Four kinds of frequently used commercial proteinases with different active sites were tested for the hydrolyzation of the soybean meal, and the combination of the acidic proteinase and the neutral proteinase showed the best results. In a fermentation medium containing 100 g L-1 glucose and 200 g L-1 hydrolysate, Bacillus sp. H-18W produced 21.84 g L-1 acetoin with an ee value of 96.25% at 60 h. This is the first report of using a thermophilic strain to produce chiral acetoin by microbial fermentation. Thermophilic fermentation can reduce the risk of bacterial contamination and can save cooling water. Using soybean meal hydrolysate and glucose as feedstocks, this work provides an economical and alternative method for the production of chiral pure acetoin.

[Investigation on secondary metabolites of endophytic fungus Talaromyces purpurogenus hosted in Tylophora ovate].

Eight compounds,(R)-2-[5-(methoxycarbonyl)-4-methyl-6-oxo-3,6-dihydro-2H-pyran-2-yl]acetic acid(1),(3S,4R)-3,4-dihydro-3,4-epoxy-5-hydroxynaphthalen-1(2H)-one(2),(-)-mitorubrinol(3),(-)-mitorubrin(4),(±)-asperlone A(5), terreusinone(6), verrucisidinol(7) and cerebroside C(8) were isolated from the endophytic fungus Talaromyces purpurogenus by using various column chromatographic techniques. Their structures were identified by NMR, MS, CD and optical rotation. Compounds 1 and 2 were new compounds. Their anti-diabetic activities in vitro were evaluated, and compound 1 showed moderate inhibitory activity toward XOD at 10 µmol·L~(-1) with the inhibition rate of 69.9%.

Nonadride and Spirocyclic Anhydride Derivatives from the Plant Endophytic Fungus Talaromyces purpurogenus.

Six new nonadride derivatives (1-6) and three new spirocyclic anhydride derivatives (7-9) were isolated from the endophytic fungus Talaromyces purpurogenus obtained from fresh leaves of the toxic medicinal plant Tylophora ovata. The structures of these compounds were determined by spectroscopic analyses including 1D and 2D NMR, HRESIMS, and ECD techniques. Maleic anhydride derivatives 1-9 were evaluated for their in vitro anti-inflammatory activities. Compound 1 showed significant inhibitory activity against NO production in LPS-induced RAW264.7 cells with an IC50 value of 1.9 µM. Compounds 2 and 6 showed moderate inhibitory activities toward XOD and PTP1b, respectively, at 10 µM with inhibition rates of 67% and 76%.

Sesquiterpenes from an Endophytic Aspergillus flavus.

Eight new cadinene-sesquiterpenes (1-8), one eudesmane-sesquiterpene (9), and three known compounds (10-13) were isolated from an endophytic fungus, Aspergillus flavus, which was isolated from a toxic medicinal plant, Tylophora ovata. Their structures were elucidated by interpretation of spectroscopic data, and absolute configurations determined according to the specific rotation and electron circular dichroism methods. Compounds 4-8, 11, and 12 exhibited latent hepatic protection effects at 10 µM, and compound 12 selectively inhibited the proliferation of MCF-7 breast cancer cells with an IC50 values of 2.6 µM.

Artificial Neural Network: A Method for Prediction of Surgery-Related Pressure Injury in Cardiovascular Surgical Patients.

PURPOSE: The aim of this study was to build an artificial neural network (ANN) model for predicting surgery-related pressure injury (SRPI) in cardiovascular surgical patients. DESIGN: Prospective cohort study. SUBJECTS AND SETTING: One hundred forty-nine patients who had cardiovascular surgery were included in the study. This study was conducted in a 1000-bed teaching hospital in Eastern China where 250 to 350 cardiac surgeries are performed each year. METHODS: We performed a prospective cohort study among consecutive patients undergoing cardiovascular surgery between January and December 2015. The ANN model was built based on possible SRPI risk factors. The model performance was tested by a receiver operating characteristic curve and the C-index. A C-index from 0.5 to 0.7 is classified as having low accuracy, 0.7 to 0.9 as having moderate accuracy, and 0.9 to 1.0 as having high accuracy. We also compared the actual SRPI incidences based on the ANN stratification. RESULTS: Thirty-seven of 147 patients developed SRPIs, yielding an incidence rate of 24.8% (95% CI, 18.1-32.6). The C-index was 0.815, which showed the ANN model had a moderate prediction value for SRPI. According to the ANN model, the SRPI predicting incidence ranged from 6.4% to 67.7%. Surgery-related pressure injury incidences were significantly different among 3 risk groups stratified by the ANN (P < .05). CONCLUSION: We established an ANN model that provides moderate prediction of SRPI in patients undergoing cardiovascular surgical procedures. Identification and additional associated factors should be incorporated into the ANN model to increase its predictive ability.

[Investigations on secondary metabolites of endophyte Diaporthe sp. hosted in Tylophora ovata].

One new compound (2S, 3S)-2,3-dihydroxybutyl 2-hydroxy-3,5,6-trimethylbenzoate (1) and six known compounds xylariphthalide A (2), convolvulol (3), cis-4-hydroxy-6-deoxytalone (4), phomoxydienes B (5), 5,6-dihydroxy-2,3,6-trimethylcyclohex-2-enone (6), trans-cyclo-(D-tryptophanyl-L-tyrosyl) (7) were isolated from Diaporthe sp., an endophytic fungus hosted in the leaves of the toxic Chinese folk medicine Tylophora ouata, using the combination methods of silica gel column chromatography, medium-pressure ODS column chromatography and RP-preparative HPLC. The structure of compound 1 was elucidated by NMR and MS data analyses. The absolute configurations were established according to the ¹H-NMR data and exciton chirality method. Compound 1 inhibited the activation of human lung fibroblasts MRC-5 cells by 64.0% at 10 µmol·L⁻¹. The MTT assay showed that compounds 2 and 4 displayed cytotoxic activity against human tumor cell lines BGC-823 cells with IC50 values of 1.5 and 8.6 µmol·L⁻¹, respectively.

Enzymatic synthesis of aroma acetoin fatty acid esters by immobilized Candida antarctica lipase B.

OBJECTIVE: To enzymatically synthesize aroma acetoin fatty acid esters, useful as flavor and fragrance ingredients in foods. RESULTS: Immobilized Candida antarctica lipase B (CALB), performed significantly better than lipases from Rhizopus niveus and Candida rugosa in carrying out the esterification of acetoin and fatty acids. C4-C12 straight chain fatty acids were suitable acyl donors and CALB had a strong preference for longer straight chains up to ten carbon atoms. Higher temperatures, 40-60 °C, and higher acetoin/fatty acid molar ratios favored the conversion. The maximum yield of acetoin octanoate obtained was (51 ± 1) % after 24 h reaction time in hexane with 0.25 M octanoic acid, 5:1 excess acetoin and an enzyme concentration of 6 g/mol fatty acid at 60 °C. The enzyme activity declined at a steady rate during reuse at 60 °C and after the 10th cycle, 65 % of initial activity was still be retained. CONCLUSION: This is the first report of acetoin fatty acid ester synthesis by biological method and CALB has been shown to be effective for the lipase-catalyzed esterification of acetion and C4-C12 straight chain fatty acids.

Thermophilic production of polyhydroxyalkanoates by a novel Aneurinibacillus strain isolated from Gudao oilfield, China.

Polyhydroxyalkanoates (PHAs) are usually biosynthesized using mesophilic strains, but the fermentation processes often suffer from bacterial contamination. This work reports the screening of thermophilic bacteria capable of producing PHAs under elevated temperatures to reduce the contamination risk. Strain XH2 was isolated from an oilfield and identified as Aneurinibacillus sp. by morphology, physiological-biochemical characterization, and 16S rDNA phylogenetic analysis. This strain can produce PHA granules, which was detected by Nile red staining and transmission electron microscopic imaging. At 55 °C, 111.6 mg l(-1) of PHA was produced in a fermentation medium containing glucose, peptone, and yeast extract. If peptone was removed from the medium, the yield of PHA would be enhanced by 2.4 times. The main monomers of the PHA product were identified to be 3-hydroxybutyrate and 3-hydroxyvalerate with a molar ratio of 17.2:1 by gas chromatography-mass spectroscopy (GC-MS) and nuclear magnetic resonance analyses. Two minor homologues, 3-hydroxyoctanoate, and 3-hydroxy-4-phenylbutanoate, were tentatively identified by GC-MS as well. This is the first report of thermophilic PHA bacterial producer from the Firmicutes phylum.

MHO or MUO? White adipose tissue remodeling.

In this review, we delve into the intricate relationship between white adipose tissue (WAT) remodeling and metabolic aspects in obesity, with a specific focus on individuals with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). WAT is a highly heterogeneous, plastic, and dynamically secreting endocrine and immune organ. WAT remodeling plays a crucial role in metabolic health, involving expansion mode, microenvironment, phenotype, and distribution. In individuals with MHO, WAT remodeling is beneficial, reducing ectopic fat deposition and insulin resistance (IR) through mechanisms like increased adipocyte hyperplasia, anti-inflammatory microenvironment, appropriate extracellular matrix (ECM) remodeling, appropriate vascularization, enhanced WAT browning, and subcutaneous adipose tissue (SWAT) deposition. Conversely, for those with MUO, WAT remodeling leads to ectopic fat deposition and IR, causing metabolic dysregulation. This process involves adipocyte hypertrophy, disrupted vascularization, heightened pro-inflammatory microenvironment, enhanced brown adipose tissue (BAT) whitening, and accumulation of visceral adipose tissue (VWAT) deposition. The review underscores the pivotal importance of intervening in WAT remodeling to hinder the transition from MHO to MUO. This insight is valuable for tailoring personalized and effective management strategies for patients with obesity in clinical practice.

Inhibition of tumor growth and alteration of associated macrophage cell type by an HO-1 inhibitor in breast carcinoma-bearing mice.

Heme oxygenase-1 [HO-1, also called heat shot protein 32 (HSP32)] can specifically metabolize heme to carbon monoxide, biliverdin, and ferrous iron and plays an important role in the processes of anti-inflammation, tissue protection, and antioxidative stress reaction. It has been reported that HO-1 can promote tumorigenesis and metastasis of many tumors. However, the detailed mechanisms of how HO-1 affects tumor progress are not clear. Here, we used ZnPPIX (a specific inhibitor of HO-1) to evaluate its potential effects on mouse breast cancer and tumor-associated macrophages (TAMs). We found out that mouse 4T1 breast cancer growth can be effectively suppressed through inhibition of HO-1 in vitro and in vivo. Moreover, in the 4T1 mouse model, when HO-1 was suppressed in TAMs, alternatively activated macrophages (M2 type) switched to classically activated macrophages (M1 type). In conclusion, 4T1 breast cancer growth was modulated by HO-1 expression. Furthermore, inhibition of HO-1 may induce tumor-associated immune response by activating TAMs' alternative proliferation. These data suggest that HO-1 may be an important target of breast cancer treatment.

[Study on tissue distribution of borneol in mice by intravenous and intranasal administrations].

OBJECTIVE: To develop a GC-FID method to determine borneol's concentration in mouse tissues, and to investigate the tissue distribution after intravenous and intranasal administrations of borneol. METHOD: Mouse brains, hearts, livers, spleens, lungs and kidneys were collected at 1, 3, 5, 10, 20, 30, 60, 90, 120 min after administration of borneol with the dose of 30.0 mg x kg(-1). The drug in tissues was extracted with ethyl acetate, and borneol's concentration detected by GC, with octadecane as the internal standard. RESULT: The calibration curve showed a good linear relationship. Extraction recoveries, inter-day and intra-day precisions and stability were in conformity with the analytical requirements of biological samples. Borneol was mainly distributed in most tissues, more in heart, brain and kidney, and less in liver, spleen and lung. CONCLUSION: The established GC-FID method is applicable for content determination of borneol in tissues. After intravenous and intranasal administrations in mice, borneol is mainly distributed in abundant blood-supply tissues. After intranasal administration, brain tissues showed the highest target coefficient and target effectiveness.