Xylarkarynone A and B: Two Bioactive Eremophilane Sesquiterpenes from Xylaria sp. HHY-2.

A new compound xylarkarynone A (1), a first reported natural product compound xylarkarynone B (2) and eight known compounds (3-10) were isolated from Xylaria sp. HHY-2. Their structures were elucidated by spectroscopic methods, DP4+ probability analyses and electronic circular dichroism (ECD) calculations. The bioactivities of isolated compounds were assayed. Compound 1 exhibited obvious activity against A549 cells with an IC50 value of 6.12±0.28 µM. Additionally, compound 1 showed moderate antifungal activities against Plectosphaerella cucumerina and Aspergillus niger with minimum inhibitory concentrations (MICs) of both 16 µg/mL, which was at the same grade with positive control nystatin. Most compounds exhibited varying degrees of inhibitory activity against P. cucumerina, indicating that Xylaria sp. has potential as inhibitors against P. cucumerina.

Association between new plasma inflammatory markers and risk of colorectal neoplasms in individuals over 50 years old.

OBJECTIVE(S): The prognostic value of systemic cytokine profiles and inflammatory markers in colorectal cancer were explored by several studies. We want to know more about inflammatory biomarkers in colorectal adenoma and early cancer. METHOD: The level of 38 inflammatory markers in the plasma of 112 adenoma patients, 72 Tis-T1 staging of colorectal carcinoma patients, 34 T2-T4 staging of colorectal carcinoma patients and 53 normal subjects were detected and compared. RESULT(S): Eight inflammatory biomarkers (Eotaxin, GCSF, IL-4, IL-5, IL-17E, MCP-1, TNF-α and VEGF-A) have higher plasma concentrations in colorectal adenoma and cancer patients compared with normal participants over 50 years old. CONCLUSION(S): Inflammatory markers may have the prognostic value for colorectal adenoma and early-stage carcinoma.

A novel standalone microfluidic device for local control of oxygen tension for intestinal-bacteria interactions.

The intestinal environment is unique because it supports the intestinal epithelial cells under a normal oxygen environment and the microbiota under an anoxic environment. Due to importance of understanding the interactions between the epithelium and the microbiota, there is a strong need for developing representative and simple experimental models. Current approaches do not capture the partitioned oxygen environment, require external anaerobic chambers, or are complex. Another major limitation is that with the solutions that can mimic this oxygen environment, the oxygenation level of the epithelial cells is not known, raising the question whether the cells are hypoxic or not. We report standalone microfluidic devices that form a partitioned oxygen environment without the use of an external anaerobic chamber or oxygen scavengers to coculture intestinal epithelial and bacterial cells. By changing the thickness of the device cover, the oxygen tension in the chamber was modulated. We verified the oxygen levels using several tests: microscale oxygen sensitive sensors which were integrated within the devices, immunostaining of Caco-2 cells to determine hypoxia levels, and genetically encoded bacteria to visualize the growth. Collectively, these methods monitored oxygen concentrations in the devices more comprehensively than previous reports and allowed for control of oxygen tension to match the requirements of both intestinal cells and anaerobic bacteria. Our experimental model is supported by the mathematical model that considered diffusion of oxygen into the top chamber. This allowed us to experimentally determine the oxygen consumption rate of the intestinal epithelial cells under perfusion.

Secondary Metabolites from Annulohypoxylon sp. and Structural Revision of Emericellins A and B.

Seven previously undescribed compounds were isolated from the endophytic fungus Annulohypoxylon sp. KYG-19 (family Xylariaceae), including three gymnomitrane-type sesquiterpenes xylariacinols A, B, and D (1, 2, and 4), one bisabolane-type sesquiterpene annulnol F (6), one phenol derivative lariacinol G (7), and two polyhydroxy compounds hypoxylonols H and I (8 and 9), together with two known gymnomitrane-type sesquiterpenes emericellin A (3) and 3-gymnomitren-15-ol (5). The assignments of their structures was determined by extensive spectroscopic and spectrometric analysis, acetonide analysis, Mosher's method, and X-ray crystallography. In addition, the structures of emericellins A and B, which were reported to possess an unprecedented tricyclo[4, 4, 2, 1]hendecane scaffold, were revised by comparing their spectroscopic data with those of 1 and 3. Compounds 1 and 4 exhibited antibacterial activity against Escherichia coli with minimum inhibitory concentrations of 4 and 2 µg/mL, respectively.

A New Highly Oxygenated Polyketide Derivative from Trichoderma sp. and Its Antifungal Activity.

A new highly oxygenated polyketide derivative, trichodersine (1), together with fourteen known compounds (2-15) were isolated from Trichoderma sp. MWTGP-04. The structure of trichodersine (1) was established based on comprehensive spectroscopic data analysis, and biogenesis argument. The results of double culture experiments indicated that the strain exhibited potential antifungal activity. The antifungal activities of all isolated compounds were evaluated, among them compound 1 exhibited remarkable antifungal activities against Fusarium solani, Plectosphaerella cucumerina, Alternaria panax, and Aspergillus niger, with minimum inhibitory concentrations (MICs) of 4, 4, 16, and 32 µg/mL, respectively. In addition, the antifungal experiments of polyketide derivatives (1-3) disclosed that their degree of oxidation was a key factor affecting the antifungal activity.

Oxycodone attenuates vascular leak and lung inflammation in a clinically relevant two-hit rat model of acute lung injury.

BACKGROUND: Oxycodone is a synthetic opioid receptor agonist that exerts antinociceptive activity via κ-, µ- and δ-opioid receptors (KOR, MOR and DOR, respectively). Activation of MOR has been reported to provide protection against acute lung injury (ALI). We hypothesized that pretreatment with oxycodone would attenuate lung injury at the level of alveolar tight junctions (TJs) and aquaporins (AQPs) and investigated this possibility in a two-hit model of ALI induced by lipopolysaccharide (LPS) and mechanical ventilation (MV). METHOD: Male Sprague Dawley rats and A59 cells were divided into 6 groups: the control group, ALI group, oxycodone-pretreated group, and oxycodone/κ-, µ-, or δ-opioid receptor antagonist-pretreated groups. The rats were pretreated with oxycodone 30 min before intravenous injection of LPS and then allowed to recover for 24 h prior to MV, establishing a two-hit model of ALI. The cells were similarly treated with oxycodone (with or without antagonists) 30 min after exposure to lipopolysaccharide. The cells were cyclically stretched 24 h later to mirror the in vivo MV protocol. RESULTS: Oxycodone alleviated the histological lung changes in the rats with ALI and decreased pulmonary microvascular permeability both in vivo and in vitro. Oxycodone upregulated the expression of claudin-5, ZO-1, AQP1, and AQP5 but downregulated the expression of TNF-α, IL-1ß, TLR4, NF-κB, MMP9, and caspase-3 and suppressed endothelial apoptosis in vivo and in vitro. These protective effects of oxycodone were partly eliminated by KOR and MOR antagonists but not by DOR antagonists. CONCLUSION: Oxycodone pretreatment appears to act via κ- and µ-opioid receptors to ameliorate LPS- and MV-induced lung injury by suppressing inflammation and apoptosis, and this protective effect might be mediated through the inhibition of the TLR4/NF-κB pathways.

Ketamine ameliorates ischemia-reperfusion injury after liver autotransplantation by suppressing activation of Kupffer cells in rats.

This study aimed to investigate the protective effects of ketamine against hepatic ischemia-reperfusion (I/R) injury by suppressing activation of Kupffer cells (KCs) in rat liver autotransplantation. Male Sprague-Dawley rats were randomized into 3 groups (n = 10 each). Group I, the sham group, received saline. Group II received saline and underwent orthotopic liver autotransplantation (OLAT). Group III received 10 mg/kg ketamine and underwent OLAT. Blood samples were obtained at 3, 6, 12, and 24 h after I/R, and following ALT, AST, LDH, IL-6, TNF-α, IL-1ß, and IL-10 in serum were detected. Model rats were sacrificed at the indicated time points and the graft liver tissues were evaluated histologically. KCs were isolated from rat liver tissues, and inflammatory products and proteins of NF-κB signaling pathway were detected using quantitative RT-PCR and Western blotting. Our results showed that ketamine significantly decreased ALT, AST, LDH, IL-6, TNF-α, and IL-1ß levels and increased IL-10 level. Furthermore, ketamine alleviated the histopathology changes, by less KC infiltration and lower hepatocyte apoptosis. Moreover, activity of NF-κB signaling pathway in KCs was suppressed. In addition, production of pro- and anti-inflammatory factors is consistent with the results in tissues. Ketamine ameliorated I/R injury after liver transplantation by suppressing activation of KCs in rats.

Posttreatment with propofol attenuates lipopolysaccharide-induced up-regulation of inflammatory molecules in primary microglia.

BACKGROUND: Activation of microglia is involved in a broad range of neuroinflammatory diseases. Suppression of microglial activation may, therefore, contribute to alleviate the progression of neuroinflammatory diseases. It has been reported that propofol has a potent anti-inflammatory property. In the present study, we investigated the effects of posttreatment with propofol on the production of inflammatory molecules in lipopolysaccharide (LPS)-stimulated microglia. MATERIALS AND METHODS: Microglia were exposed to various concentrations (25, 50, 100, 250 µM) of propofol for 1 h after LPS stimulation for 24 h. The levels of proinflammatory mediators inducible nitric oxide synthase (iNOS)/nitric oxide (NO), cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were measured. RESULTS: Propofol at a concentration of 25 µM did not affect the production of proinflammatory mediators, which was enhanced by LPS. At the concentrations of 50, 100, and 250 µM, propofol significantly inhibited LPS-mediated production of NO, PGE2, TNF-α, and IL-1ß and the expression of iNOSmRNA, COX-2mRNA, TNF-α mRNA, and IL-1ß mRNA. CONCLUSIONS: These results suggest that propofol, at clinically relevant concentrations, can reduce inflammatory responses in LPS-induced inflammation in activated microglia and might be an intravenous anesthetic of choice when patients with neuroinflammatory diseases require sedation and/or general anesthesia.

Transduced PEP-1-heme oxygenase-1 fusion protein protects against intestinal ischemia/reperfusion injury.

BACKGROUND: Heme oxygenase-1 (HO-1) has been shown to have antioxidant and anti-apoptotic properties. The present study transduced HO-1 protein into intestinal tissues using PEP-1, a cell-penetrating peptide, and investigated its potentiality in prevention against intestinal ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: PEP-1-HO-1 fusion protein was administered intravenously to explore the time and dose characteristics through measuring serum HO-1 levels. Twenty-four male Sprague-Dawley rats were randomly divided into three groups: sham, intestinal I/R (II/R), II/R + PEP-1-HO-1 fusion protein (HO). The model was established by occluding the superior mesenteric artery for 45 min followed by 120 min reperfusion. In HO group, PEP-1-HO-1 was administered intravenously 30 min before ischemia, whereas animals in sham and II/R groups received the equal volume of physiological saline. After the experiment, the intestines were harvested for determination of histologic injury, wet/dry ratio, enzyme activity, apoptosis, and His-probe protein (one part of PEP-1-HO-1). RESULTS: Levels of serum HO-1 were dose- and time-dependent manner after intravenous injection of PEP-1-HO-1. I/R caused deterioration of histologic characteristics and increases in histologic injury scoring, wet/dry ratio, myeloperoxidase activity, malondialdehyde, and intestinal apoptosis. These changes were also accompanied by a decrease in superoxide dismutase activity (P < 0.05). PEP-1-HO-1 treatment significantly reversed these changes (P < 0.05). Furthermore, His-probe protein expression was only detected in PEP-1-HO-1-treated animals. CONCLUSION: Treatment of PEP-1-HO-1 attenuates intestinal I/R injury, which might be attributable to its antioxidant and anti-apoptotic roles of HO-1.

[Retracted] Methylene blue relieves the development of osteoarthritis by upregulating lncRNA MEG3.

[This retracts the article DOI: 10.3892/etm.2018.5918.].

Dexmedetomidine attenuates lipopolysaccharide-induced proinflammatory response in primary microglia.

BACKGROUND: Neuroinflammation mediated by microglia has been implicated in delirium. Suppression of microglial activation may therefore contribute to alleviate delirium. It has been reported that dexmedetomidine (DEX) has a potent anti-inflammatory property. In the present study, we investigated the effects of DEX on the production of proinflammatory mediators in lipopolysaccharide-stimulated microglia. MATERIALS AND METHODS: The concentrations of DEX were chosen to correspond to 1, 10, and 100 times of clinically relevant concentration (i.e., 1, 10, and 100ng/mL). The levels of proinflammatory mediators, such as inducible nitric oxide synthase or nitric oxide, prostaglandin E(2), interleukin 1ß, and tumor necrosis factor α, were measured. RESULTS: DEX at 1ng/mL did not affect the production of proinflammatory mediators. DEX at 10 and 100ng/mL significantly inhibited the release of nitric oxide, prostaglandin E(2), interleukin 1ß, and tumor necrosis factor α and the expression of inducible nitric oxide synthase messenger RNA. CONCLUSIONS: These results suggest that DEX is a potent suppressor of lipopolysaccharide-induced inflammation in activated microglia and may be a potential therapeutic agent for the treatment of intensive care unit delirium.

Postoperative impairment of cognitive function in old mice: a possible role for neuroinflammation mediated by HMGB1, S100B, and RAGE.

BACKGROUND: Postoperative cognitive dysfunction, a common complication after surgery in elderly patients, is an increasing and largely underestimated problem without a defined etiology. Neuroinflammation plays an important role in the pathogenesis of postoperative cognitive dysfunction. The present study sought to investigate the role of neuroinflammation mediated by high-mobility group box 1 (HMGB1), S100B, and the receptor for advanced glycation end product (RAGE) in cognitive dysfunction after partial hepatectomy in aged mice. MATERIALS AND METHODS: Old C57BL/6 mice were randomly divided into three groups: normal control (n = 18), anesthetic (n = 66), and surgery (n = 66). The mice in the surgery or anesthetic group received isoflurane anesthesia for either partial hepatectomy or no surgery, respectively. Cognitive function was subsequently assessed using a Y-maze. HMGB1, S100B, RAGE, interleukin-1ß, and nuclear factor-kappaB p65 levels were measured at 12 h and 1, 3, and 7 d after surgery. Immunofluorescence double labeling was performed to study the colocalization between RAGE and its ligands, HMGB1 and S100B. RESULTS: The mice's learning and memory abilities were significantly impaired at 1 and 3 d and 2 and 4 d after surgery, respectively. The expression of HMGB1, S100B, RAGE, and nuclear factor-kappaB p65 had increased significantly at 12 h and 1 and 3 d after surgery. The interleukin-1ß level was significantly increased at 1 and 3 d after surgery. The interaction of HMGB1 or S100B with RAGE was confirmed at 1 d after surgery. CONCLUSIONS: These data suggest that HMGB1, S100B, and RAGE signaling modulate the hippocampal inflammatory response and might play key roles in surgery-induced cognitive decline.

Transduction of PEP-1-heme oxygenase-1 fusion protein reduces myocardial ischemia/reperfusion injury in rats.

Recent studies have uncovered that overexpression of heme oxygenase-1 (HO-1) by induction or gene transfer provides myocardial protection. In the present study, we investigated whether HO-1 protein mediated by cell-penetrating peptide PEP-1 could confer cardioprotection in a rat model of myocardial ischemia/reperfusion (I/R) injury. Male Sprague-Dawley rats were subjected to 30 minutes of ischemia by occluding the left anterior descending coronary artery and to 120 minutes of reperfusion to prepare the model of I/R. Animals were randomized to receive PEP-1-HO-1 fusion protein or saline 30 minutes before a 30-minute occlusion. I/R increased myocardial infarct size and levels of malondialdehyde, serum tumor necrosis factor alpha, and interleukin 6 and reduced myocardial superoxide dismutase activity. Administration of PEP-1-HO-1 reduced myocardial infarct size and levels of malondialdehyde, serum tumor necrosis factor alpha, and interleukin 6 and increased myocardial superoxide dismutase and HO-1 activities. His-probe protein was only detected in PEP-1-HO-1-transduced hearts. In addition, transduction of PEP-1-HO-1 markedly reduced elevated myocardial tissue nuclear factor-κB induced by I/R. The results suggested that transduction of PEP-1-HO-1 fusion protein decreased myocardial reperfusion injury, probably by attenuating the production of oxidants and proinflammatory cytokines regulated by nuclear factor-κB.

Influence of carbon derivatives on carbon capture investments in coal-based power sector, a China perspective.

Coal-based power sector needs deep carbon emission reduction in the upcoming 20 years to fulfill China's carbon peaking and carbon neutrality pledge. Due to the low and fluctuating carbon price in the emission trading system, decarbonization projects are risky and face massive potential losses. To promote decarbonization investment, a lot of policies of subsidy have been set forth. However, market instruments, which could be efficient and motivating for market entities, should have received more attention. In this article, the influence of carbon derivatives on decarbonization investment and financing is analyzed for different technology progresses and price trajectories. Results show that carbon futures and options have de-risking ability, lowering expected variation and financial cost, and consequently, making decarbonization project feasible. For advanced technology and optimistic outlook, investment can be feasible with 42-66% debt share when options are available. For the base case and neutral price outlook, derivatives can pull subsidy down by around 1%.

Both extracellular vesicles from helicobacter pylori-infected cells and helicobacter pylori outer membrane vesicles are involved in gastric/extragastric diseases.

Bacterial-derived extracellular vesicles (EVs) have emerged as crucial mediators in the cross-talk between hosts and pathogens, playing a significant role in infectious diseases and cancers. Among these pathogens, Helicobacter pylori (H. pylori) is a particularly important bacterium implicated in various gastrointestinal disorders, gastric cancers, and systemic illnesses. H. pylori achieves these effects by stimulating host cells to secrete EVs and generating internal outer membrane vesicles (OMVs). The EVs derived from H. pylori-infected host cells modulate inflammatory signaling pathways, thereby affecting cell proliferation, apoptosis, cytokine release, immune cell modification, and endothelial dysfunction, as well as disrupting cellular junctional structures and inducing cytoskeletal reorganization. In addition, OMVs isolated from H. pylori play a pivotal role in shaping subsequent immunopathological responses. These vesicles incite both inflammatory and immunosuppressive reactions within the host environment, facilitating pathogen evasion of host defenses and invasion of host cells. Despite this growing understanding, research involving H. pylori-derived EVs remains in its early stages across different domains. In this comprehensive review, we present recent advancements elucidating the contributions of EV components, such as non-coding RNAs (ncRNAs) and proteins, to the pathogenesis of gastric and extragastric diseases. Furthermore, we highlight their potential utility as biomarkers, therapeutic targets, and vehicles for targeted delivery.

Phytotoxic meroterpenoids with herbicidal activities from the phytopathogenic fungus Pseudopestalotiopsis theae.

The fungus Pseudopestalotiopsis theae isolated from the fresh leaves of Illigera celebica, has been reported to be a pathogenic fungus that can cause gray blight on tea leaves, a disease characterized by the appearance of necrotic lesions on tea leaves. The pathogenic substances in this fungus have not been clearly identified. Considering the possible involvement of specialized metabolites in symptom appearance, a chemical investigation of specialized metabolites on P. theae was conducted, resulting in the isolation of eight meroterpenoids, including six undescribed biscognienynes G-L and two known ones (biscognienynes B and D). The structures of these new compounds were characterized by extensive NMR spectroscopic and HR-ESI-MS data, and their absolute configurations were elucidated by ECD calculations. Except for biscogniyne L, all the isolated biscognienynes showed different degrees of phytotoxicity to tea in vivo, thereby revealing for the first time the substances in P. theae that cause tea gray blight. Inspired by the fact that phytotoxins produced by pathogenic fungus are an effective resource for designing natural and safe bioherbicides, when assayed the herbicidal activity through Petri dish bioassays, biscognienynes G-J showed phytotoxic effects against seed germination and seedling growth of Setaria viridis, strongly inhibiting seed germination percentage and radicle and germ lengths of seedlings. The results of this study demonstrated the great potential of biscognienynes G-J to be proposed and developed as ecofriendly herbicides.

Steroids and dihydroisocoumarin glycosides from Xylaria sp. by the one strain many compounds strategy and their bioactivities.

The fungus Xylaria sp. KYJ-15 was isolated from Illigera celebica. Based on the one strain many compounds (OSMAC) strategy, the strain was fermented on potato and rice solid media, respectively. As a result, two novel steroids, xylarsteroids A (1) and B (2), which are the first examples of C28-steroid with an unusual ß- and γ-lactone ring, respectively, along with two new dihydroisocoumarin glycosides, xylarglycosides A (3) and B (4), were identified. Their structures were elucidated by spectroscopic methods, X-ray diffraction and electronic circular dichroism (ECD) experiments. All isolated compounds were evaluated for cytotoxicity, DPPH radical scavenging activity, acetylcholinesterase inhibitory and antimicrobial effect. Compound 1 exhibited potent AChE inhibitory activity with an IC50 value of 2.61 ± 0.05 µmol·L-1. The ß-lactone ring unit of 1 is critical for its AChE inhibitory activity. The finding was further confirmed through exploring the interaction of 1 with AChE by molecular docking. In addition, both compounds 1 and 2 exhibited obvious antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) of 2 µg·mL-1. Compounds 3 and 4 exhibited antibacterial activities against Staphylococcus aureus with MICs of 4 and 2 µg·mL-1, respectively, which also exhibited DPPH radical scavenging activity comparable to the positive control with IC50 values of 9.2 ± 0.03 and 13.3 ± 0.01 µmol·L-1, respectively.

A new cyclopentenone derivative from Trichoderma atroviride HH-01.

A new cyclopentenone derivative, atrovinol (1), together with ten known compounds (2-11) were isolated from Trichoderma atroviride HH-01, an endophytic fungus from Illigera rhodantha (Hernandiaceae). Their structures were identified by HRESIMS, 1 D/2D NMR, and electronic circular dichroism (ECD) spectra. Compound 1 exhibited moderate inhibitory activity against Staphylococcus aureus and Bacillus subtilis with MIC values of 8.0 µg/mL and 16.0 µg/mL, respectively.

Guided isolation of secondary metabolites from Nectria sp. MHHJ-3 by molecular network strategy.

The fungus Nectria sp. MHHJ-3 was isolated from Illigera rhodantha. A molecular networking-guided the secondary metabolites investigation of Nectria sp. MHHJ-3 led to the isolation of ten metabolites (1-10), including two new naphthalenone derivatives, nectrianaphthalenones A (1) and B (2), and two new steroids, nectriasteroids A (3) and B (4). Their structures were elucidated by extensive spectroscopic analysis including the HRESIMS, 1D/2D NMR and electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway for 1-2 was proposed. Compounds 1 and 2 exhibited moderate acetylcholinesterase (AChE) inhibitory activities. Compounds 3 and 4 showed significant cytotoxic activity against selected tumor cells. Particularly, compound 3 exhibited the strongest activity against A549 cells with an IC50 value of 13.73 ± 0.03 µM, which was at the same grade with that of positive control cisplatin.

An Ultraflexible Electrode Array for Large-Scale Chronic Recording in the Nonhuman Primate Brain.

Single-unit (SU) recording in nonhuman primates (NHPs) is indispensible in the quest of how the brain works, yet electrodes currently used for the NHP brain are limited in signal longevity, stability, and spatial coverage. Using new structural materials, microfabrication, and penetration techniques, we develop a mechanically robust ultraflexible, 1 µm thin electrode array (MERF) that enables pial penetration and high-density, large-scale, and chronic recording of neurons along both vertical and horizontal cortical axes in the nonhuman primate brain. Recording from three monkeys yields 2,913 SUs from 1,065 functional recording channels (up to 240 days), with some SUs tracked for up to 2 months. Recording from the primary visual cortex (V1) reveals that neurons with similar orientation preferences for visual stimuli exhibited higher spike correlation. Furthermore, simultaneously recorded neurons in different cortical layers of the primary motor cortex (M1) show preferential firing for hand movements of different directions. Finally, it is shown that a linear decoder trained with neuronal spiking activity across M1 layers during monkey's hand movements can be used to achieve on-line control of cursor movement. Thus, the MERF electrode array offers a new tool for basic neuroscience studies and brain-machine interface (BMI) applications in the primate brain.