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Two-dimensional (2D) organic–inorganic hybrid materials have attracted widespread attention for photodetection. Moreover, such materials with broadband photoluminescence and strong photocurrent response are still rare. Here, we report two new semiconducting 2D organic–inorganic hybrid materials, namely {PbII2I6[PbII(TETA)]}n (1Pb) and {PbII3I8[PbII(TETA)]}n (2Pb), where TETA = triethylenetetramine, with broadband yellow-green emission. Both compounds are soluble in DMF and yield high surface coverage films through spin coating. Strikingly, the photocurrent responses of such thin films show ca. 600 and 700 nA cm−2 difference between Ilight and Idark for 1Pb and 2Pb, respectively. To the best of our knowledge, 1Pb and 2Pb showed among the highest current obtained in 2D lead iodide hybrid materials under a low voltage (0.7 V). Moreover, 1Pb and 2Pb are stable under heat, moisture and light, which may provide realistic applications for light detection.

Targeting poly(ADP-ribose) polymerase1/2 (PARP1/2) is a promising strategy for the treatment of pancreatic cancer with breast cancer susceptibility gene (BRCA) mutation. Inducing the deficiency of homologous recombination (HR) repair is an effective way to broaden the indication of PARP1/2 inhibitor for more patients with pancreatic cancer. Bromodomain-containing protein 4 (BRD4) repression has been reported to elevate HR deficiency. Therefore, we designed, synthetized, and optimized a dual PARP/BRD4 inhibitor III-16, with a completely new structure and high selectivity against PARP1/2 and BRD4. III-16 showed favorable synergistic antitumor efficacy in pancreatic cancer cells and xenografts by arresting cell cycle progression, inhibiting DNA damage repair, and promoting autophagy-associated cell death. Moreover, III-16 reversed Olaparib-induced acceleration of cell cycle progression and recovery of DNA repair. The advantages of III-16 over Olaparib suggest that dual PARP/BRD4 inhibitors are novel and promising agents for the treatment of advanced pancreatic cancer.

Most cancer therapies are suffering from side effects to varying degrees, which might compromise the body functions and long-term health of patients. Balancing treatment efficacy and side effects has become a priority. Inspired by the concept that cellular ion homeostasis can lead to apoptosis, we developed a novel therapeutic strategy by incorporating the K+ transporter valinomycin into liposomes (Lipo-VM). Valinomycin is a naturally occurring polypeptide showing good biodegradation in vivo with reduced long-term side effects. Lipo-VM facilitates the K+ efflux of cells and triggers a caspase-dependent pathway of apoptosis by causing the collapse of mitochondrial membrane potential. With the help of a liposome-based nano-delivery system, Lipo-VM shows enhanced cell uptake and accumulation at the tumor site, which results in significant inhibition of tumor growth in a liver cancer model. The proposed valinomycin-anchored liposome provides an efficient and safe approach for cancer therapy.

SARM1, an executioner in axon degeneration, is an autoinhibitory NAD-consuming enzyme, composed of multiple domains. NMN and its analogs, CZ-48 and VMN, are the only known activators, which can release the inhibitory ARM domain from the enzymatic TIR domain. Here, we document that acid can also activate SARM1, even more efficiently than NMN, possibly via the protonation of the negative residues. Systematic mutagenesis revealed that a single mutation, E689Q in TIR, led to the constitutive activation of SARM1. It forms a salt bridge with R216 in the neighboring ARM, maintaining the autoinhibitory structure. Using this 'acid activation' protocol, mutation K597E was found to inhibit activation, while H685A eliminated SARM1 catalytic activity, revealing two distinct inhibitory mechanisms. The protocol has also been applied to differentiate two classes of chemical inhibitors. NAD, dHNN, disulfiram, CHAPS, and TRX-100 mainly inhibited the activation process, while nicotinamide and Tweens mainly inhibited SARM1 catalysis. Taken together, we demonstrate a new mechanism for SARM1 activation and decipher two distinct inhibitory mechanisms of SARM1.

A Cd(ΙI)-based luminescent coordination polymer, namely [Cd(L)2(H2O)2]n (1), has been synthesized by 1-(tetrazo-5-yl)-4-(triazo-1-yl)benzene ligand (HL) and structurally characterized. The selectiv...

Co(II) and Cu(II) complexes, [Co2(H2L)2(phen)2(H2O)4](H2O)2 (1) and [Cu2(L)0.5(phen)2Cl2]n (2) [H4L = 5,5'-(diazene-1,2-diyl)diisophthalic acid, phen = 1,10-phenanthroline], have been solvothermall...

Triptolide (TP), an active component of Tripterygium wilfordiiHook. f. (TWHF), has been widely used for centuries as a traditional Chinese medicine. However, the clinical application of TP has been restricted due to multitarget toxicity, such as hepatotoxicity. In this study, 28 days of oral TP administration (100, 200, or 400 μg·kg-1·d-1) induced the occurrence of cholestasis in female Wistar rats, as evidenced by increased serum levels of γ-glutamyl transpeptidase (γ-GGT), alkaline phosphatase (ALP) and hepatic total bile acids (TBAs). In addition, the heptocyte polarity associated with the strcture of tight junctions (TJs) was disrupted in both rats and sandwich-cultured primary hepatocytes. Immunoblotting revealed decreased expression of the TJ-associated proteins occludin, claudin-1, and zonula occludens protein (ZO-1), and downregulated mRNA levels of these TJs was also detected by real-time PCR. An immunofluorescence analysis showed abnormal subcellular localization of occludin, claudin-1 and ZO-1, which was also confirmed by transmission electron microscopy. Moreover, the concentration of FITC-dextran, a marker of paracellular penetration, was found to increase rapidly in bile increased rapidly (within 6 minutes) after treatment with TP, which indicated the functional impairment of TJs. Taken together, these results suggest that the administration of TP for 28 consecutive days to rats could induce cholestatic injury in the liver, and the increased paracellular permeability might play an important role in these pathological changes.

Cross-ply unidirectional laminates made of ultra-high molecular weight polyethylene fibers are widely used as components of bullet-proof vests. To simulate the delamination process of the material under penetration, we constructed a numerical mechanical model, which was validated by tests using 7.62 × 39 mm rifle bullets penetrating laminates of different thicknesses. The results show that the delamination region is essentially diamond-shaped. The simulated delamination region is in good agreement with the experimental data. It is found that the delamination region increases with the compression modulus along the fiber direction. The delamination region increases when the shear strength between the fabric layers decreases; However, it is little influenced by the normal strength. The delamination region of the front face of the laminate is little influenced by the failure strain of the material and the initial velocity of the bullet. The delamination region of the back face increases with the failure strain and decreases with the initial velocity.

Methyl orange (MO) is a main organic water pollutants that has been attracted a lot of attention; it can be degraded under photoirradiation in the presence of H2O2. Herein, we developed two Cu(I)-b...

Brassinosteroids (BRs) are plant steroidal phytohormones that play an important role in plant growth, stress responses, and adaptation. BIP130 is a BR-INSENSITIVE 1 (BRI1)-interacting protein, and BIP130 phosphorylation by OsMPK1 upregulates abscisic acid (ABA)-induced antioxidant defense in rice protoplasts. However, studies on BIP130-induced modulation of plant responses to salt stress are lacking. This study investigated the function of BIP130 in response to salt stress in transgenic rice (Oryza sativa L.). We assayed the relative BIP130 transcript levels in wild-type (WT) plants with NaCl treatment and observed the effects on scavenging reactive oxygen species (ROS) in transgenic plants. Changes in ABA content in transgenic plants were also analyzed. NaCl treatment upregulated relative transcript and protein levels of BIP130 in WT plants. The bip130 RNA interference (RNAi) rice mutants displayed a hypersensitive response to salt stress, while BIP130-overexpressing plants showed significant enhancement of salt tolerance, which was confirmed by changes in survival rates, antioxidant enzyme activities, H2O2 levels, and electrolyte leakage. RNA-sequencing analysis showed that BIP130 upregulates nine ABA-related genes (OsPSY2, OsNCED3, OsNCED4, OsCIPK6, OsCIPK16, OsCIPK31, OsEDL3, OsbZIP23, OsHVA22). ABA content significantly increased in BIP130-overexpressing and significantly decreased in bip130-RNAi plants. Therefore, BIP130 is involved in NaCl-induced antioxidant defense and enhances salt stress tolerance by modulating ABA biosynthesis and ROS scavenging in rice.

In virtue of the dual-ligand strategy, a novel Zn(II)-organic coordination polymer [Zn(tipb)(bpda)0.5·(OH)]n (1) (tipb = 1,3,5-tris(p-imidazolylphenyl)benzene, H2bpda = 4,4′-biphenyldicarboxylic ac...

Vitamin B6 is necessary to maintain normal metabolism and immune response, especially the anti‐inflammatory immune response. However, the exact mechanism by which vitamin B6 plays the anti‐inflammatory role is still unclear. Here, we report a novel mechanism of preventing excessive inflammation by vitamin B6 via reduction in the accumulation of sphingosine‐1‐phosphate (S1P) in a S1P lyase (SPL)‐dependent manner in macrophages. Vitamin B6 supplementation decreased the expression of pro‐inflammatory cytokines by suppressing nuclear factor‐κB and mitogen‐activated protein kinases signalling pathways. Furthermore, vitamin B6–reduced accumulation of S1P by promoting SPL activity. The anti‐inflammatory effects of vitamin B6 were inhibited by S1P supplementation or SPL deficiency. Importantly, vitamin B6 supplementation protected mice from lethal endotoxic shock and attenuated experimental autoimmune encephalomyelitis progression. Collectively, these findings revealed a novel anti‐inflammatory mechanism of vitamin B6 and provided guidance on its clinical use.

Summary Objectives Interferons (IFNs) play multifunctional roles in host defense against infectious diseases by inducing IFN-stimulated genes (ISGs). However, little is known about how ISGs regulate host immune response to Mycobacterium tuberculosis (Mtb) infection, the major cause of tuberculosis (TB). Methods We thus profiled the potential effects and mechanisms of eight Mtb-induced ISGs on Mtb infection by RNA interference in human macrophages (Mφs) derived from peripheral blood monocytes (hMDMs) and THP-1 cell line derived Mφs (THP-1-Mφs). Results MxA silencing significantly decreased intracellular Mtb infection in Mφs. Mechanistically, MxA silencing promoted inflammatory cytokines IL-1β, IL-6 and TNF-α production, and induced NF-κB p65 activation. Pharmacological inhibition of NF-κB p65 activation or gene silencing of NF-κB p65 blocked the increased production of IL-1β, IL-6 and TNF-α and restored Mtb infection by MxA silencing. Furthermore, pharmacological inhibition of TAK1 and IKKα/β blocked NF-κB p65 activation and subsequent production of pro-inflammatory cytokines by MxA silencing. Isoniazid (INH) treatment and MxA silencing could promote TAK1-IKKα/β-NF-κB signaling pathway activation and combat Mtb infection independently. Conclusions Our results reveal a novel role of MxA in regulating TAK1-IKKα/β-NF-κB signaling activation and production of antimicrobial inflammatory cytokines upon Mtb infection, providing a potential target for clinical treatment of TB.

The role of epithelial V‐like antigen 1 (EVA1) has been well studied in thymic development and homostasis; however, its putative relationship with cancer remains largely unknown. Therefore, here we investigated the role of EVA1 in hepatocellular carcinoma. Interestingly, EVA1 expression was significantly increased in hepatocellular carcinoma (HCC) and was also associated with a poor prognosis and recurrence in HCC patients. Overexpression of EVA1 promoted cell growth, invasion and migration in vitro. Consistently, knockdown of EVA1 expression inhibited proliferation and migration in vitro, while repressing metastasis of HCC cells in vivo. RNA‐seq analysis indicated that EVA1 is able to upregulate the expression of genes in the ERBB3‐PI3K pathway. Accordingly, an increased level of AKT phosphorylation was detected in HCC cells after EVA1 overexpression. LY294002, a PI3K inhibitor, inhibited AKT phosphorylation and rescued the tumor‐promoting effect of EVA1 overexpression. Altogether, the present study has revealed the oncogenic role of EVA1 during HCC progression and metastasis through the ERBB‐PI3K‐AKT signaling pathway, reiterating the potential use of EVA1 as a therapeutic target and/or prognostic marker for HCC., In this study, EVA1 was identified as an oncogene and promoted tumor progression and metastasis in HCC by targeting the ERBB‐PI3K‐AKT pathway. Thus, the present study revealed that EVA1 could be a potential prognostic indicator and molecular target for HCC therapies.

To investigate the effects of gastrodin (GAS) on methamphetamine (MA)-induced conditioned place preference (CPP) in rats and explore its potential mechanisms. MA (10 mg/kg) was initially injected intraperitoneally (i.p.) in rats, after which they were administered either MA or saline alternately from day 4 to 13 (D4–13) for 10 days, followed by treatment with GAS (10 or 20 mg/kg, i.p.) on D15–21 for 7 days. The rats underwent CPP testing after MA and GAS treatment. In vitro, SH-SY5Y cells were exposed to MA (2.0 mM) for 24 h, followed by treatment with GAS (2.0 or 4.0 mM) for 24 h. The expression levels of PKA, P-PKA, CREB, and P-CREB proteins in the prefrontal cortex, nucleus accumbens, and ventral tegmental area of MA-induced CPP rats and in SH-SY5Y cells were detected by Western blot analysis. The MA-induced CPP rat model was successfully established. The administration of MA stimulated a significant alteration in behavior, as measured by the CPP protocol. After treatment with GAS, the amount of time rats spent in the MA-paired chamber was significantly reduced. Results also showed that MA increased the expression levels of PKA, P-PKA, CREB, and p-CREB proteins in the prefrontal cortex, nucleus accumbens, and ventral tegmental area of CPP rats and in SH-SY5Y cells (p

Dihydroartemisinin (DHA) is a potent anti-cancer drug that has limited clinical applications due to poor water solubility and low bioavailability. We designed a biodegradable poly(ethylene glycol) methyl ether-poly(ε-caprolactone) (MPEG-PCL) micelle carrier for DHA using the self-assembly method. The DHA/MPEG-PCL nanoparticles were spherical with an average particle size of 30.28 ± 0.27 nm, and released the drug in a sustained manner in aqueous solution. The drug-loaded nanoparticles showed dose-dependent toxicity in HeLa cells by inducing cycle arrest and apoptosis. Furthermore, compared to free DHA, the DHA/MPEG-PCL nanoparticles showed higher therapeutic efficacy and lower toxicity in vivo, and significantly inhibited tumor growth and prolonged the survival of tumor-bearing nude mice. In addition, the tumor tissues of the DHA/MPEG-PCL-treated mice showed a marked decline in the in situ expression of proliferation and angiogenesis markers. Taken together, the self-assembled DHA/MPEG-PCL nanoparticles are a highly promising delivery system for targeted cancer treatment.

Blockade of the NOD-like receptor protein 3 (NLRP3) inflammasome has been shown to be effective in halting the progression of non-alcoholic steatohepatitis (NASH). Antrodia cinnamomea is a well-known indigenous medicine used by Taiwanese aboriginal tribes. However, its effect on NASH remains unclear. This study aimed to examine the mechanistic insight of Antrodia cinnamomea extract (ACE) in both in vitro and in vivo models of NASH. Murine RAW264.7 macrophages and human hepatocellular carcinoma HepG2 cells were treated with the indicated concentration of ACE 30 minutes prior to stimulation with lipopolysaccharide (LPS) for 24 h. Levels of inflammatory markers, NLRP3 inflammasome, components, and endoplasmic reticulum (ER) stress markers were analyzed by Western blotting. For the in vivo experiments, male C57BL/6 mice weighing 21–25 g were fed a methionine/choline deficient (MCD) diet along with vehicle or ACE (100 mg/kg) for 10 consecutive days. The serum glutamate pyruvate transaminase (SGPT) levels of the mice were measured. The liver tissues from the mice underwent histological analysis (hematoxylin and eosin staining), and the levels of inflammatory markers, NLRP3 inflammasome components, and autophagy-related proteins were evaluated. ACE significantly inhibited NLRP3 inflammasome activation in vitro and in vivo. In addition, ACE attenuated the severity of MCD-induced steatohepatitis, reduced the levels of oxidative stress markers, and ameliorated inflammatory responses, but restored autophagic flux. Based on these findings, Antrodia cinnamomea could be developed into an anti-non-alcoholic fatty liver disease/NASH agent.

The P1/HC-Pro viral suppressor of potyvirus suppresses posttranscriptional gene silencing (PTGS). The fusion protein of P1/HC-Pro can be cleaved into P1 and HC-Pro through the P1 self-cleavage activity, and P1 is necessary and sufficient to enhance PTGS suppression of HC-Pro. To address the modulation of gene regulatory relationships induced by turnip mosaic virus (TuMV) P1/HC-Pro (P1/HC-ProTu), a comparative transcriptome analysis of three types of transgenic plants (P1Tu, HC-ProTu, and P1/HC-ProTu) were conducted using both high-throughput (HTP) and low-throughput (LTP) RNA-Seq strategies. The results showed that P1/HC-ProTu disturbed the endogenous abscisic acid (ABA) accumulation and genes in the signaling pathway. Additionally, the integrated responses of stress-related genes, in particular to drought stress, cold stress, senescence, and stomatal dynamics, altered the expressions by the ABA/calcium signaling. Crosstalk among the ABA, jasmonic acid, and salicylic acid pathways might simultaneously modulate the stress responses triggered by P1/HC-ProTu. Furthermore, the LTP network analysis revealed crucial genes in common with those identified by the HTP network in this study, demonstrating the effectiveness of the miniaturization of the HTP profile. Overall, our findings indicate that P1/HC-ProTu-mediated suppression in RNA silencing altered the ABA/calcium signaling and a wide range of stress responses.

Submicron-thick yttrium iron garnet films were grown on a gadolinium gallium garnet substrate by pulsed laser deposition. The morphology and crystal structure results show that the submicron-thick film has a flat surface, low surface roughness of ∼ 0.5 ± 0.05 nm and good epitaxy with the (444) plane. Magnetic hysteresis loops also indicate that the submicron-thick film has great soft magnetic properties. However, the ferromagnetic resonance (FMR) spectrum shows that the submicron-thick film has multiple resonance peaks. The angular dependence of the FMR response of the 10-nm-thick, 100-nm-thick and 525-nm-thick films shows that peaks 1 (at low field) and 2 (at high field) observed in the 525-nm-thick film spectrum originate from the internal layer and the outer layer of the films, respectively. Lastly, the angular dependence of the FMR linewidth shows that the lowest FMR linewidth occurred at an angle between the direction of the static field and film normal of 50°.

Postoperative adhesions are the most common complications of peri-abdominal surgery; they not only affect the patient's quality of life but also increase the risk of a subsequent surgery. The use of implantable dressings to physically block surgical wounds is the primary solution to prevent postoperative adhesions. In this study, we prepared naproxen nanoparticles that were loaded with chitosan hydrogel (CS/Nap hydrogel) to prevent postoperative adhesions. Our data confirmed that the prepared CS/Nap hydrogel was thermosensitive and suitable for injection. The efficacy of anti-adhesion in a rat model revealed that the hydrogel effectively separated from the wounds of the abdominal wall and cecum. On day 7 postsurgery, the wounds were completely covered by a new epithelial layer, whereas wounds in the negative control group were glued together. Additionally, the in vivo toxicity study showed that the CS/Nap hydrogel had fewer toxic and side effects on major tissues and organs, including the liver, spleen, heart, lung, and kidney. We showed that a drug delivery system based on CS/Nap hydrogel has the potential not only to prevent postoperative abdominal adhesions and relieve pain but also to contribute to the administration of the hydrophobic drug naproxen.

In this work, yttrium iron garnet films were prepared on a Ga3Gd5O12 substrate by pulsed laser deposition. The dependence of target grain size on the morphology, crystallinity, and magnetism of films was investigated. Firstly, X-ray diffraction revealed that the fine grain size of the target was beneficial for increasing the crystallinity of films. Secondly, scanning electron microscopy and roughness measurements displayed the film prepared by the small grain size of the target has better morphology and lower roughness. Lastly, magnetic hysteresis loops and ferromagnetic resonance measurements further shown that a good microstructure and fine grain size of target facilitated the growth of film with greater magnetic properties. Consequently, YIG film deposited by 1.0 μm-target has magnetic properties with a high saturation magnetization of 155 emu/cm3, a low saturation magnetic field of 1077 Oe, and low ferromagnetic resonance linewidth of 42 Oe.

Six new compounds, hyperpatulones A–F (1–6), along with ten additional known related derivatives (7–16), were isolated from Hypericum patulum (Guttiferae). Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR), X-ray crystallography, electronic circular dichroism (ECD) spectroscopy and Rh2(OCOCF3)4-induced ECD. All compounds were tested for their cytotoxic activities on human HepG-2, HeLa, MCF-7, and A549 cell lines via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compound 5 exhibited significant cytotoxicities against HepG-2, HeLa and A549 cell lines with IC50 values of 9.52 ± 0.27, 11.87 ± 0.22 and 12.63 ± 0.12 μM, respectively.

Polyvinyl butyral (PVB) was used in the Al(OH)3/carbon black/ethanol slurries by the three-roll mixing to prepare AlN powder using the carbothermal reduction–nitridation (CRN) process in the experiments. The effects of PVB addition on the synthesis of AlN powder were studied by viscosity, tap density, XRD, SEM and TG measurements. The results showed that the PVB layer covering on the surface of Al(OH)3 particles reduced the viscosity of Al(OH)3/carbon/ethanol slurry and increased the dispersion homogeneity of Al(OH)3/carbon raw powder. The tap densities of the Al(OH)3/carbon mixtures after three-roll milling could be increased with the increase in PVB addition. In the CRN process, most of the PVB covering Al(OH)3 particles evaporated and supplied the passage for nitrogen removal to the particles. Based on the experimental data, the role of PVB on the mixing and CRN process was discussed.

Acute myeloid leukemia (AML) is a malignant cancer of the hematopoietic system. Although the effectiveness of arsenic compounds has been recognized and applied clinically, some patients are still found resistant to this chemotherapy. In this study, we investigated that a synthetic thyroid hormone analog (TA), 2-iodo-4-nitro-1-(o-tolyloxy) benzene, had a strong apoptosis effect on U937 cells. U937 cells were treated with TA, and examinted the generation of reactive oxygen species (ROS), dysfunction of mitochondria, expression of pro-apoptosis and anti-apoptosis, and cleavage of caspase-3 and Poly (ADP-ribose) polymerase (PARP). Further, it is also evaluated that insight molecular mechanism and signaling pathways involved in the study. It is found that TA significantly induced apoptosis in U937 cells through production of ROS, dysfunction of mitochondria, and activation of caspase cascade. It was also observed that MAPK signaling pathway including ERK, JNK, and P38 signals are involved in the induction of apoptosis. Moreover, marked activation of autophagy and ER stress markers such as LC3, P62, Beclin1 and GRP78, CHOP were observed, respectively. Pretreatment with ER stress inhibitor tauroursodeoxycholic acid (TUDCA) and autophagy inhibitor 3-Methyladenine (3-MA) have successfully attenuated and aggravated TA-induced apoptosis, respectively. We further confirmed the active involvement of ER stress and autophagy signals. In conclusion, TA induced apoptosis through ER stress and activation of autophagy, and the latter is not conducive to TA-induced cell death. Our results may provide a new insight into the strategic development of novel therapy for the treatment of AML.

Apigenin, identified as 4′, 5, 7-trihydroxyflavone, is a natural flavonoid compound that has many interesting pharmacological activities and nutraceutical potential including anti-inflammatory and antioxidant functions. Chronic, low-grade inflammation and oxidative stress are involved in both the initiation and progression of hypertension and hypertension-induced cardiac hypertrophy. However, whether or not apigenin improves hypertension and cardiac hypertrophy through modulating NADPH oxidase-dependent reactive oxygen species (ROS) generation and inflammation in hypothalamic paraventricular nucleus (PVN) has not been reported. This study aimed to investigate the effects of apigenin on hypertension in spontaneously hypertensive rats (SHRs) and its possible central mechanism of action. SHRs and Wistar-Kyoto (WKY) rats were randomly assigned and treated with bilateral PVN infusion of apigenin or vehicle (artificial cerebrospinal fluid) via osmotic minipumps (20 μg/h) for 4 weeks. The results showed that after PVN infusion of apigenin, the mean arterial pressure (MAP), heart rate, plasma norepinephrine (NE), Beta 1 receptor in kidneys, level of phosphorylation of PKA in the ventricular tissue and cardiac hypertrophy, perivascular fibrosis, heart level of oxidative stress, PVN levels of oxidative stress, interleukin 1β (IL-1β), interleukin 6 (IL-6), iNOS, monocyte chemotactic protein 1 (MCP-1), tyrosine hydroxylase (TH), NOX2 and NOX4 were attenuated and PVN levels of interleukin 10 (IL-10), superoxide dismutase 1 (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67) were increased. These results revealed that apigenin improves hypertension and cardiac hypertrophy in SHRs which are associated with the down-regulation of NADPH oxidase-dependent ROS generation and inflammation in the PVN.

Malignant ascites indicate the presence of malignant cells in the peritoneal cavity that lower patient survival and reduce quality of life. Current chemotherapy regimens suffer from the dilution of ascites and rapid metabolism limiting their therapeutic efficacy. The storage and sustained release of drugs at the tumor site represents a promising strategy to improve drug efficacy. The aim of this study was to develop injectable hyaluronic acid hydrogel containing polymeric gemcitabine nanoparticles and cisplatin for the local treatment of malignant ascites through a dual sustained drug release pattern. Cell uptake assays showed that the drug-loaded nanoparticles readily entered tumor cells. Apoptosis and cell cycle analysis showed that the hydrogel system could enhance tumor cell apoptosis and arrest more cells in the G1 phase. In vivo experiments indicated that mice treated with the drug-loaded hydrogels manifested the most significant efficacy in ascites volume, tumor nodules, body weight, abdominal circumference, and survival. The expression of Ki-67 and CD31 also significantly decreased compared with other groups, indicative of anti-tumor activity. In addition, intraperitoneal administration of the hydrogel system led to no significant damage to vital organs. These findings confirm the clinical potential of the drug-loaded hydrogel system for the treatment of malignant ascites.

Mycotoxin prevalence in food is a global public health issue, that could impose severe economic burdens. To prevent risk of exposure to mycotoxins, it is of great importance to develop selective, sensitive, and reliable methods to monitor mycotoxin levels in food samples. Recent advances in nanotechnology have produced many nanomaterials with unique physical features and extensive effort has been exerted to apply these nanomaterials in mycotoxin determination. Many specific aptamers, which have distinct advantages such as uniform synthesis, low cost, customizable modification, and chemical stability, have been developed to endow nanomaterials with target selective properties. Given the merits of these materials, aptamer-based nanomaterials for mycotoxin detection have received extensive attention from researchers. This review focuses on recent advances in aptamer nanomaterial-based sensing strategies used for mycotoxin analysis in food samples in the past five years. Representative examples of aptamer nanomaterial-based sensors for specific mycotoxin detection are described. The future challenges and opportunities regarding the use of aptamer-based nanomaterials to assist in the control of mycotoxins and other food contaminants are also discussed.

Multi-drug chemotherapy has been one of the most popular strategies for the treatment of malignant tumors, and has achieved desirable therapeutic outcomes. The objective of the present study is to develop biodegradable PCEC nanoparticles (NPs) for the co-delivery of paclitaxel (PTX) and curcumin (CUR), and investigate the antitumor effect of the drug delivery system (DDS: PTX-CUR-NPs) against breast cancer both in vitro and in vivo. The prepared PTX-CUR-NPs had a small size of 27.97 ± 1.87 nm with a low polydispersity index (PDI, 0.197 ± 0.040). The results exhibited slow release of PTX and CUR from the DDS without any burst effect. Further, the PTX-CUR-NPs displayed a dose-dependent cytotoxicity in MCF-7 cells with a higher apoptosis rate (64.29% ± 1.97%) as compared to that of free drugs (PTX + CUR, 34.21% ± 0.81%). The cellular uptake study revealed that the drug loaded PCEC polymeric nanoparticles were more readily uptaken by tumor cells in vitro. To evaluate the in vivo anti-tumor effect, the PTX-CUR-NPs were intravenously administered to BALB/c nude mouse xenografted with MCF-7 cells and the results exhibited significant inhibition of tumor growth with prolonged survival time and reduced side effect when compared with free drugs (PTX + CUR). Moreover, the administration of PTX-CUR-NPs treatment led to lower Ki67 expression (p 0.05), and enhanced TUNEL positivity (higher apoptosis, p 0.01) in tumor cells as compared to other treatment groups, suggesting the therapeutic efficacy of the DDS. Altogether, the present study suggests that the DDS PTX-CUR-NPs could be employed for the effective treatment of breast cancers in near future.

The PDGF receptor is mock-coupled with a known active compound, and 14 novel skeleton candidate compounds were designed and synthesized. The structure was confirmed by 1H NMR, 13C NMR and MS. The i...

Melatonin, a safe endogenous hormone and a natural supplement, has recently been recognized to have antiproliferative effects and the ability to sensitize cells to other anticancer therapies. Phenylarsine oxide (PAO) has anticancer potential but it is considered as a toxic agent. In this study we combined melatonin to reduce the toxicity while securing the anti-cancer effects of PAO. Cell viability was determined by MTT assay, whereas cytotoxic assays were performed using an LDH cytotoxicity assay kit. Cell cycle analysis, Annexin V/PI staining, the mitochondrial membrane potential (MMP), mitochondrial calcium and reactive oxygen species (ROS) generation were analyzed using flow cytometry. Sytox stained cells were visualized by fluorescence microscopy and the expression of proteins was detected by western blotting. Melatonin increased the anticancer potential of PAO by decreasing the cell viability and increasing LDH release in various cancer cells. The mode of cell death was determined to be typical apoptosis, as evidenced by Annexin V/PI-stained cells, PARP cleavage, and caspase-3 activation, and with significant modulations in the expression of proapoptotic, antiapoptotic and cell cycle-related proteins. ROS generation played a critical role in induction of cell death by this combined treatment, which is validated by reversal of cytotoxicity upon cotreatment with NAC. Furthermore, the activation of MAPKs, especially JNK, contributed to the induction of cell death, accompanied by endoplasmic reticulum stress and autophagy, affirmed by the abrogation of cytotoxicity after JNK-IN-8 and TUDCA application. Melatonin showed promising potential as a chemotherapeutic agent in combination with PAO to achieve a better anticancer response.

TiO2 exposed high energy crystal plane (001) was prepared by the sol-gel process using butyl titanate as the titanium source and hydrofluoric acid as the surface control agent. Ag-TiO2 was prepared by depositing Ag on the crystal plane of TiO2 (101) with a metal halide lamp. The surface morphology, interplanar spacing, crystal phase composition, ultraviolet absorption band, element composition, and valence state of the samples were characterized by using field emission scanning electron microscopy (FESEM), transmission electron microscope (TEM), X-ray diffraction (XRD), ultraviolet-visible absorption spectrum (UV-Vis-Abs), and X-ray photoelectron spectroscopy (XPS), respectively. The formation mechanism of high energy crystal plane (001) was discussed, and the photocatalytic activities were evaluated by following degradation of methyl orange. The results show that TiO2 exposed the (001) crystal plane with a ratio of 41.8%, and Ag can be uniformly deposited on the crystal plane of TiO2 (101) by means of metal halide lamp deposition. Under the same conditions, the degradation rate of methyl orange by deposited Ag-TiO2 reaches as much as 93.63% after 60 min using the metal halide lamp (300 W) as an illuminant, 81.89% by non-deposited samples and 75.20% by nano-TiO2, causing a certain blue shift in the light absorption band edge of TiO2. Ag-TiO2 has the best photocatalytic performance at a pH value of 2.

In this study, biogenic iron sulfide nanoparticles (FeS NPs) were synthesized by Shewanella and used for Cr(VI) removal. To control the size of FeS NPs, the biological S(-II) releasing rate was proposed as the key parameter in Fe(III) reduction and was subtly tuned with the aid of a kinetic model. Field emission scanning electron microscope (FESEM) observation revealed that gradually increased S(-II) releasing rate lead to the formation of FeS NPs with size from 30 nm to 90 nm. Impressively, the biogenic FeS NPs with 30–40 nm showed high removal rate and large removal capacity (565.6 mg/g) for removal of aqueous Cr(VI). Further analyses revealed that the improved performance of small FeS NPs was ascribed to the reduced passivation of FeS. Therefore, this study provided a facile approach for size-controlled biosynthesis of FeS NPs, and demonstrated the promise to use biogenic FeS NPs for chromate remediation.

Pilot-scale three-stage surface flow constructed wetlands (SFCWs) planted with Myriophyllum aquaticum were constructed to study the organics removal performance from lagoon-pretreated swine wastewater. The removal performance of organics in the SFCWs was evaluated using deterministic and probabilistic methods and the results were consistent. The SFCWs achieved a relatively high removal efficiency (79.0–82.7%) for a wide influent COD concentration range (456–1010 mg L−1). No significant difference (p > 0.05) of COD removal efficiency and first-order removal rate constant among the various strengths of influent suggested that the present loading rates (2.74–6.06 g m−2 d−1) have not yet reached the maximum removal capacity of the SFCWs. The mean emission fluxes of methane from the SFCW units fed with different strengths of wastewater were 25–1210 mg m−2 d−1. A significantly positive correlation (p

With the assistance of solvated aluminum cation as the template, a novel iodoargentate was successfully constructed. The two-dimensional anionic framework displays high performance on cationic dye methylene blue (MB+) capture with good efficiency and selectivity via ion exchange. Moreover, the adsorbed MB+ can be readily and easily released in the presence of Na+.

Two copper(I) iodide compounds with formula of {[Cu2I2(2-mna)]·DMA} (1) and {[CuI(6-mna)]·DMSO} (2) (2-mna = 2‑mercaptonanicotinic acid; 6-mna = 6‑mercaptonanicotinic acid; DMA = dimethylacetamide; DMSO = dimethyl sulfoxide) have been prepared by reaction and evaporation between CuI and 2-mna/6-mna at room temperature. Four Cu atoms in 1 are linked by I− ions and 2-mna ligands into [Cu4I4(2-mna)2] units which are further linked into a 1D inorganic-organic chain by sharing Cu I bonds. In 2, thiolate sulfur of 6-mna adopts μ2-coordination modes to bridge two Cu atoms, forming [Cu2(6-mna)2] building units, which are further connected by I− ions into 1D chain structure. It is worth mentioning that the Cu⋯Cu distances in 1 and 2 are shorter than the sum of the van der Waals radii of copper(I) (2.80 A), implying the metal-metal bonding interactions. Interestingly, compounds 1 and 2 display blue and red fluorescence emission bands in the solid state, respectively. In particular, compound 2 exhibits the capability to selectively detect Fe3+ ion as a fluorescence “turn-off” sensor.

While one dimensional1H nuclear magnetic resonance (1D1H-NMR) spectroscopy is one of the most important and convenient method for measuring conformation change in biomacromolecules, characterization of protein dynamics in large membrane protein complexes by 1D1H-NMR remains challenging, due to the difficulty of spectra assignment, low signal-to-noise ratio (S/N) and the need for large amount of protein. Here we report the site-specific incorporation of 4-trimethylsilyl phenylalanine (TMSiPhe) into proteins, through genetic code expansion inEscherichia colicells, and the measurement of multiple conformational states in membrane protein complex by 1D1H-NMR. The unique up-field1H-NMR chemical shift of TMSiPhe, highly efficient and specific incorporation of TMSiPhe enabled facile assignment of the TMSiPhe1H-NMR signal, and characterization of multiple conformational state in a 150 kilodalton (kD) membrane protein complex, using only 5 μM of protein and 20 min spectra accumulation time. This highly efficient and convenient methods should be broadly applicable for the investigation of dynamic conformation change of protein complexes.

F&ndash, TiO2 was prepared by a simple precipitation method using titanium sulfate as the titanium source, hydrogen fluoride as the fluorine source and ammonia as the precipitant. CdS/F&ndash, TiO2 composites were prepared by hydrothermal synthesis of CdS and F&ndash, TiO2. The surface morphology, crystal phase composition, ultraviolet absorption band, fluorescence intensity, element composition, valence state, specific surface and pore structure of the samples were characterized by using field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), ultraviolet visible absorption spectrum (UV-Vis-Abs), Molecular fluorescence spectrophotometer (PL) and X-Ray photoelectron spectroscopy (XPS) and Surface area analyzer (BET), respectively. The effects of the dosage of the photocatalyst, pH value, the concentration of methyl orange and the addition of H2O2 on the photocatalytic performance were investigated with methyl orange solution as the target degradation product. The results showed the optimum condition for photodegradation of methyl orange by 1% CdS/F&ndash, TiO2 is that the pH value, the solid-liquid ratio, the concentration of methyl orange and the dosage of H2O2 is 2, 2 g/L, 10 mg/L and 3%, respectively. Under the same conditions, the degradation rate of methyl orange by 1% CdS/F&ndash, TiO2 was 93.36% when 300 W metal halide lamp was irradiated for 20 minutes, which was significantly higher than that of F&ndash, TiO2. CdS has a significant effect on the morphology, crystallinity, grain size and the compound probability of electrons and holes after the F&ndash, TiO2 modification. The composite causes a significant red shift at the edge of the F&ndash, TiO2 light absorption band. The photocatalytic degradation of methyl orange by 1% CdS/F&ndash, TiO2 follows the Langmuir-Hinshelwood first-order kinetic model.

Hyperthermia is one therapeutic tool for damaging and killing cancer cells, with minimal injury to normal tissues. However, its cytotoxic effects alone are insufficient for quantitative cancer cell death. To overcome this limitation, several studies have explored non-toxic enhancers for hyperthermia-induced cell death. Capsaicin may be applicable as a therapeutic tool against various types of cancer. In the present study, we employed nonivamide, a less-pungent capsaicin analogue, to investigate its possible enhancing effects on hyperthermia-induced apoptosis; moreover, we analyzed its molecular mechanism. Treatment of U937 cells at 44 °C for 15 min, combined with nonivamide 50 μM, revealed enhancement of apoptosis. Significant increases in reactive oxygen species generation, mitochondrial dysfunction, and cleaved caspase-3 were observed during the combined treatment; these were accompanied by an increase in pro-apoptotic Bcl-2 family proteins and a decrease in anti-apoptotic Bcl-2 proteins. In addition, significant increases in p-JNK and p-p38 were detected, following the combined treatment. In conclusion, nonivamide enhanced hyperthermia-induced apoptosis via a mitochondrial-caspase dependent pathway. The underlying mechanism may include elevation of intracellular reactive oxygen species, mitochondrial dysfunction, and increased activation of JNK and p38.

In this study, an asymmetric membrane containing an electrospun copper benzene-1,3,5-tricarboxylate (Cu-BTC)/poly(vinyl alcohol) (PVA) pre-selective layer and a dense PVA separation layer (M CuBTC ) was fabricated. The existence of the electrospun Cu-BTC/PVA composite nanofibre layer coated on a dense PVA membrane was observed to significantly improve the separation performance and membrane permeability by serving as a hydrophilic pre-selective barrier during the application of the M CuBTC membrane to the pervaporation dehydration of aqueous 1,4-dioxane solutions. The M CuBTC membrane demonstrated improved pervaporation performance, with a total permeation flux of 87.69 g/m 2 h, a separation factor of up to 1852.32, a water permeance of 2102.87 gpu, and a water selectivity of 1365.96. It is interesting to note that due to the addition of the electrospun pre-selective layer, the permeation flux demonstrated by the M CuBTC membrane was double of that of the dense PVA membrane, while the separation factor increased from 392.65 to 1852.32.

An efficient “umpolung relay” three-component regioselective coupling reaction of triphenylamine/carbazole derivatives with C60 and indoles was developed. This new methodology includes a one-pot, double polarity inversion of C60, and thus achieved a cascade reaction of aromatic (indole) nucleophilic addition and electrophilic substitution of arenes (triphenylamine/carbazole). This protocol features high regioselectivity, broad substrate scope, and excellent functional group tolerance that includes bromo, ester, nitro, cyano, formyl, and N–H groups on the arenes.

A facile strategy for fabrication of conductive polyaniline (PANI) nanoflower modified carbon cloth electrode was developed and its application for microbial energy harvesting was also demonstrated. By simply tuning the concentration of aniline monomer, uniformly distributed PANI nanoflowers assembled from PANI nanoflakes anchored on the surface of carbon cloth electrode were fabricated with in-situ polymerization. Electrochemical and spectral analyses indicated that the synthesized PANI nanoflower was in conductive emeraldine salt form. Electrochemical impedance spectroscopy (EIS) analysis revealed PANI nanoflower modification reduced the charge transfer resistance of carbon cloth electrode, indicating the PANI nanoflower had excellent electrochemical activity. Furthermore, the PANI nanoflower modified electrode was used as the anode of microbial fuel cells (MFC), which delivered 2.6 and 6.5 times higher voltage and power output than these of pristine carbon cloth electrode, respectively. This work provided a controllable synthesis strategy for PANI nanostructure and demonstrated its promise in microbial energy harvesting.

In this work, 16 kinds of novel deep eutectic solvents (DESs) composed of polyethylene glycol (PEG) and quaternary ammonium salts, were coupled with Aqueous Biphasic Systems (ABSs) to extract RNA. The phase forming ability of ABSs were comprehensively evaluated, involving the effects of various proportions of DESs' components, carbon chain length and anions species of quaternary ammonium salts, average molecular weights of PEG and inorganic salts nature. Then the systems were applied in RNA extraction, and the results revealed that the extraction efficiency values were distinctly enhanced by relatively lower PEG content in DESs, smaller PEG molecular weights, longer carbon chain of quaternary ammonium salts and more hydrophobic inorganic salts. Then the systems composed of [TBAB][PEG600] and Na2SO4 were utilized in the influence factor experiments, proving that the electrostatic interaction was the dominant force for RNA extraction. Therefore, back-extraction efficiency values ranging between 85.19% and 90.78% were obtained by adjusting the ionic strength. Besides, the selective separation of RNA and tryptophane (Trp) was successfully accomplished. It was found that 86.19% RNA was distributed in the bottom phase, while 72.02% Trp was enriched in the top phase in the novel ABSs. Finally, dynamic light scattering (DLS) and transmission electron microscope (TEM) were used to further investigate the extraction mechanism. The proposed method reveals the outstanding feasibility of the newly developed ABSs formed by PEG-based DESs and inorganic salts for the green extraction of RNA.

A salicylaldehyde derivative bearing four pyridine arms, 3,5-bis(N,N-bis(2-pyridylmethyl)aminomethyl)-2,4-dihydroxybenzaldehyde (Hbpsal) as a "socket", was prepared and used to derive a series of zinc complexes with various extra anions "plugged" into their vacant site. The crystal structure and 1 H NMR spectra were noticeably influenced by the extra anions, allowing fine-tuning of the properties by "plug-and-socket"-type modification. Similar to unsubstituted salicylaldehyde, the zinc complexes reacted with primary amines to afford Schiff-base compounds. Because of the potential chirality around the coordination sphere, reaction with a chiral amine resulted in an equilibrium system between diastereomers, the potential of which as chiral sources tunable by the extra anions is discussed. Some of the complexes were further converted into zinc- or nickel-salphen (=N,N-bis(salicylidene)-1,2-phenylenediamine) complexes. The electrochemical properties of the nickel complex were slightly modified by the extra anions, whereas the photophysical properties of the zinc complex appeared unchanged.

Two N-containing hydrocarbon based polymers polyacrylonitrile (PAN) and polyaniline (PANI) were found to be able to destabilize LiBH 4 , a potential hydrogen storage material, resulting in larger hydrogen capacities of more than 10 wt% with peak dehydrogenation temperatures around 344 °C. The results suggest that a co-destabilization effect was achieved through the interaction of B H and C H bonds, which was further enhanced due to the presence of nitrogen atoms in polymers. After rehydrogenation of the dehydrogenated products, LiBH 4 was found to be regenerated to a large extent in both of the LiBH 4 +polymer composites. Detailed analysis including XRD, FTIR, DSC-TG-MS, HRTEM, Raman, XPS and solid-state 11 B MAS NMR was performed to elucidate the dehydrogenation and rehydrogenation mechanisms in these composites. The results provide considerable information about interaction mechanisms among B H, C H, N H and C N bonds and also shed lights on the enhancement of LiBH 4 dehydrogenation and reversibility.

Phytochemical investigation of the ethanol extract from the twigs and leaves of Croton tiglium led to the isolation of two new phorbol esters (1–2) and seven known ones (3–9). Their structures were elucidated by the analyses of extensive spectroscopic data (IR, MS, and 1D and 2D NMR) and comparing with related compounds. Meanwhile, compounds 1–9 were determined for their cytotoxic activities on human lung cancer cell line A549. Among them, 1–2 were inactive against the cell line A549 (IC50 > 100 μM), but compounds 3 and 7 showed weak activities.

Chronic administration of glucocorticoids has been shown to render individuals highly susceptible to mycobacterial infection and lead to reactivation of latent bacilli. However, the effect of glucocorticoids on innate anti-mycobacterial defense, especially in macrophages remains largely unknown. Here, we found that glucocorticoids inhibited the innate immune response, antimicrobial nitric oxide production and autophagy in mycobacteria-challenged macrophages. Meanwhile, maturation and acidification of mycobacterial phagosomes were attenuated in RAW264.7 cells after glucocorticoids treatment. Consequently, we observed a glucocorticoid-induced increase in the survival of intracellular mycobacteria in both primary macrophages and cell lines. Glucocorticoids treatment decreased the activation of TBK1 kinase, which promotes the maturation of autophagosomes. Inhibition of TBK1 also decreased the production of nitric oxide. Furthermore, several autophagy-related genes were down-regulated, while activation of the Akt/mTOR signaling pathway was increased after glucocorticoids treatment, which may account for autophagy inhibition during mycobacterial infection. Restoration of autophagy with the agonist rapamycin abolished glucocorticoid-mediated enhancement of mycobacterial survival, suggesting that glucocorticoids blocked anti-mycobacterial defense via autophagy inhibition. Collectively, this study demonstrates that glucocorticoids impair innate antimicrobial autophagy and promote mycobacterial survival in macrophages, which is a novel mechanism for glucocorticoid-mediated immunosuppression. Our findings may provide important clues for tuberculosis prevention.

Ethnopharmacological relevance Xiaoaiping injection, a traditional Chinese medical injection extracted from root of Marsdenia tenacissima (Roxb.) Moon, has been exclusively used on curing malignant tumor in China and as adjuvant therapeutic agent for chemotherapeutics, including paclitaxel. Aim of the study The goal of this study was to investigate the synergistic inhibitory efficacy of Xiaoaiping injection and paclitaxel on ovarian cancer. The mechanism may be associated with nuclear receptor pregnane X receptor (PXR) regulating its downstream molecules. Materials and methods In vitro, MTT assay, flow cytometry and Hoechst dyeing were used to evaluate the SK-OV-3 cell proliferation, apoptosis and cell cycle respectively. The mRNA and protein expression of PXR and its downstream CYP450 enzymes, transporters and Bcl-2 families were measured by qRT-PCR and Western blot. Rhodamine 123 efflux experiment was conducted to detect the P-gp efflux ability. PXR plasmid and PXR siRNA were transiently transfected into SK-OV-3 cells respectively to establish PXR-overexpressed or PXR-interfered cells. In vivo, xenograft tumor mice model was established by SK-OV-3 cells to estimate the antitumor effect of Xiaoaiping injection combined with paclitaxel. The expressions of PXR and its downstream molecules in tumor tissues were determined to further clarify the potential mechanism. Results Xiaoaiping injection significantly enhanced the anti-proliferation, pro-apoptosis effect of paclitaxel on SK-OV-3 cells. The synergetic effect was displayed by Xiaoaiping injection inhibiting paclitaxel-induced PXR and CAR expression, which subsequently inhibited CYP450 enzymes CYP2C8 and CYP3A4, transporter P-gp and anti-apoptotic proteins Bcl-2 and Bcl-xl in SK-OV-3 cells. In PXR-overexpressed cells, Xiaoaiping injection down-regulated the expression of PXR and its downstream molecules. The result of xenograft tumor model showed that Xiaoaiping injection combined with paclitaxel enhanced anti-tumor effect on ovarian cancer in vivo. Conclusions Xiaoaiping injection enhances anti-tumor effect of paclitaxel by inhibiting cell proliferation, inducing apoptosis process. The mechanism may be associated with Xiaoaiping injection inhibiting PXR and its downstream metabolic enzymes CYP2C8, CYP3A4, transporter P-gp and anti-apoptosis protein Bcl-2.

Candida albicans and Cryptococcus neoformans, human-pathogenic fungi found worldwide, are receiving increasing attention due to high morbidity and mortality in immunocompromised patients. In the present work, 110 fungus pairs were constructed by coculturing 16 wood-decaying basidiomycetes, among which coculture of Trametes robiniophila Murr and Pleurotus ostreatus was found to strongly inhibit pathogenic fungi through bioactivity-guided assays. A combination of metabolomics and molecular network analysis revealed that 44 features were either newly synthesized or produced at high levels in this coculture system and that 6 of the features that belonged to a family of novel and unusual linear sesterterpenes contributed to high activity with MICs of 1 to 32 μg/ml against pathogenic fungi. Furthermore, dynamic 13C-labeling analysis revealed an association between induced features and the corresponding fungi. Unusual sesterterpenes were 13C labeled only in P. ostreatus in a time course after stimulation by the coculture, suggesting that these sesterterpenes were synthesized by P. ostreatus instead of T. robiniophila Murr. Sesterterpene compounds 1 to 3 were renamed postrediene A to C. Real-time reverse transcription-quantitative PCR (RT-qPCR) analysis revealed that transcriptional levels of three genes encoding terpene synthase, farnesyl-diphosphate farnesyltransferase, and oxidase were found to be 8.2-fold, 88.7-fold, and 21.6-fold higher, respectively, in the coculture than in the monoculture, indicating that biosynthetic gene cluster 10 was most likely responsible for the synthesis of these sesterterpenes. A putative biosynthetic pathway of postrediene A to postrediene C was then proposed based on structures of sesterterpenes and molecular network analysis. IMPORTANCE A number of gene clusters involved in biosynthesis of secondary metabolites are presumably silent or expressed at low levels under conditions of standard laboratory cultivation, resulting in a large gap between the pool of discovered metabolites and genome capability. This work mimicked naturally occurring competition by construction of an artificial coculture of basidiomycete fungi for the identification of secondary metabolites with novel scaffolds and excellent bioactivity. Unusual linear sesterterpenes of postrediene A to C synthesized by P. ostreatus not only were promising lead drugs against human-pathogenic fungi but also highlighted a distinct pathway for sesterterpene biosynthesis in basidiomycetes. The current work provides an important basis for uncovering novel gene functions involved in sesterterpene synthesis and for gaining insights into the mechanism of silent gene activation in fungal defense.