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Hepatocellular carcinoma (HCC) is a primary cause of cancer mortality. PAK1 plays key roles in many types of cancers. However, the role of PAK1 in HCC is not clear. qRT-PCR and Western blotting were used to determine expressions of PAK1, Snail and epithelial mesenchymal transition (EMT)-related proteins. Luciferase reporter assay was used to measure the interaction between PAK1 and Snail. Wound healing, transwell, colony formation assays and flow cytometry were used to assess cell migration, invasion, proliferation and apoptosis. Mouse tumor xenograft model was used to determine the effect of PAK1 on tumor growth in vivo. PAK1 and Snail were up-regulated in HCC cells. PAK1 knockdown suppressed cell proliferation, migration and invasion, and increased apoptosis of HCC cells. PAK1 knockdown also inhibited tumor growth in vivo. Mechanistically, PAK1 promoted EMT by targeting Snail. Knockdown of PAK1 could up-regulate pro-apoptotic proteins but down-regulate proliferation-related proteins via suppressing β-catenin signaling pathway. PAK1 promotes EMT process by increasing Snail, and facilitates progression of HCC by activating β-catenin pathway. • PAK1 and Snail are up-regulated in HCC. • PAK1 drives EMT programs through targeting Snail in HCC. • Knockdown of PAK1 inhibits migration and invasion by repressing EMT. • Knockdown of PAK1 suppresses cell proliferation but induces apoptosis by inhibiting PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • Structural diversity of indole-diterpenoids from two co-cultured fungi was described. • These indole-diterpenoids displayed extensive biological activities. • The anti-influenza mechanism of compounds 1, 2, and 7 was further investigated. • The SAR of PTPs inhibitory activity of 1, 2, 4, 5, 9–16, and 19–21 was summarized. Co-culturing the marine-derived fungi Penicillium janthinellium with Paecilomyces formosus led to the isolation of nine new indole-diterpenes, janthinellumines A–I (1 – 9), along with twelve known analogues (10 – 21). The chemical structures including their absolute configurations of them were assigned by the analysis of extensive spectroscopic data and calculated ECD and VCD methods. These indole-diterpenoids displayed extensive biological activities, including anti-influenza A virus, protein tyrosine phosphatase (PTP) inhibitory, and anti- Vibrio activities. Among them, the anti-influenza mechanism of compounds 1 , 2 , and 7 was further investigated using neuraminidase inhibitory assay, molecular docking, and reverse genetics methods, suggesting that 1 , 2 , and 7 could interact with Arg371 of the viral neuraminidase. The structure–activity relationship (SAR) of PTPs inhibitory activity for indole-diterpene derivatives (1 , 2 , 4 , 5 , 9 – 16 , and 19 – 21) was also summarized. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatocellular carcinoma (HCC) is one of the primary causes of cancer-related death and resistance to cytotoxic chemotherapy is the major cause of mortality in HCC patients. miR-122 is a liver specific miRNA and is found to be reduced in HCC, however, the function of miR-122 in HCC chemosensitivity remains elusive. Methods We used qRT-PCR to measure expressions of miR-122, β-catenin and MDR1 in four HCC cell lines. And we assessed the effects of miR-122 or β-catenin on cell viability and apoptosis upon oxaliplatin (OXA) treatment by MTT assay and flow cytometry. In addition, we validated the interactions of miR-122/β-catenin and β-catenin/MDR1 by dual luciferase reporter assay and chromatin immunoprecipitation (ChIP). Western blotting was used to determine the protein levels of β-catenin, Wnt1 and MDR1. In the end, we verified the anti-tumor effect of miR-122 in vivo by using mouse tumor xenograft model. Results We found that miR-122 was down-regulated in HCC cells. Up-regulation of miR-122 or inhibition of Wnt/β-catenin signaling promoted HCC cells apoptosis and increased the sensitivity of HCC cells to OXA. On the molecular level, we showed that miR-122 directly targeted and suppressed Wnt/β-catenin pathway while β-catenin bound with MDR1 promoter and activated its transcription. Overexpression of miR-122 inhibited MDR1 expression via directly suppressing Wnt/β-catenin pathway. Conclusion Our study fully demonstrated that miR-122 inhibits MDR1 expression via suppression of Wnt/β-catenin pathway, thereby enhancing HCC sensitivity to OXA. Therefore, miR-122 could serve as a novel potential therapeutic target for HCC. Highlights • miR-122 is down-regulated and Wnt/β-catenin pathway is activated in HCC. • Overexpression of miR-122 increases HCC cells' sensitivity to OXA. • Overexpression of miR-122 suppresses Wnt/β-catenin pathway via targeting β-catenin. • β-catenin increases MDR1 expression by binding to the promoter of MDR1. • Overexpression of miR-122 increases OXA anti-tumor effect in vivo. [ABSTRACT FROM AUTHOR]

Cerebral ischemic-reperfusion injury as an inflammatory and microcirculation dysfunction pathological condition negatively affects the clinical outcome of stroke patients. The novel inflammatory procoagulant protein fgl2 has been reported to play a role in some inflammatory and coagulation dysregulation diseases. This study aimed to examine the relationship between fgl2 expression and infarct size in an acute cerebral ischemic-reperfusion rat model. We studied fgl2 mRNA and protein expressions in cerebral tissue and peripheral macrophages, and the expressions of several inflammatory factors (TNF-α, IL-1β, MCP-1, and IL-8) in serum samples from rats with acute cerebral ischemic-reperfusion injury. Fiber microthrombosis in situ contributed to the microvascular thrombosis in acute cerebral ischemic-reperfusion injury, and fgl2 expression tended to strongly correlate with cerebral infarct size. The expression levels of the other inflammatory factors significantly increased but weakly correlated with cerebral infarct size. These findings support the potential of fgl2 level as a novel biomarker of acute cerebral ischemic-reperfusion injury. [ABSTRACT FROM AUTHOR]

The Wuda Coalfield, Inner Mongolia suffers from serious coal fires for more than half a century. Fire-extinguishing projects have been carried out to suppress the coal fires since the last decade, but sporadic surface fires still occur and underground fires are more prevailing. Here, we used a real-time RA-915M Mercury Analyzer with modified inlet to monitor gaseous Hg concentrations in fumes emitted from boreholes that were designed to detect and control the underground coal fires. Meanwhile, offline methods were used to collect the fumes and analyze the contents of the gases including CO, CO 2 , CH 4 , C 2 H 6 , C 2 H 4 and C 2 H 2. The results showed that gaseous Hg concentrations in fumes from boreholes ranged from 6.42 ± 0.73 to 123.53 ± 34.66 ng m−3, with an average value of 49 ± 44 ng m−3. We suggest that the amounts of coal left for burning or smoldering mainly accounted for the large variation in fume Hg concentrations of underground coal fires. The gaseous Hg concentrations in near-surface air surrounding boreholes varied from 2.38 ± 0.28 to 13.10 ± 0.97 ng m−3, with a mean value of 6.68 ± 3.09 ng m−3. They were higher than the ambient air Hg concentrations measured at a background site near the Yellow River (<2 ng m−3), suggesting underground coal fires were one significant Hg pollution source. Importantly, we found that gaseous Hg concentrations in the boreholes had significantly positive correlations with temperatures and CO (a traditional coal-fire index gas) contents, implying that Hg has the potential to serve as an index gas to monitor the occurrences of underground coal fires in mining goafs. Image 1 • Gaseous Hg in underground fire fumes were measured by a RA-915M with modified inlet. • Gaseous Hg concentrations in fire fumes from the mining goaf were elevated. • Hg has the potential to monitor fire occurrence and intensity in coal mining goafs. [ABSTRACT FROM AUTHOR]

Although osimertinib, an EGFR tyrosine kinase inhibitor, has become the standard therapy for treating non-small cell lung cancer (NSCLC) patients with EGFR-activating mutation, upregulation of MCL-1 induces acquired resistance to osimertinib. Bufalin, a natural digoxin-like ingredient isolated from a traditional Chinese medicine Chan Su, has been shown to downregulate MCL-1 in NSCLC cells. However, whether bufalin reverses this acquired resistance to osimertinib in NSCLC cells remains unclear. In this study, bufalin reduced cell viability and promoted apoptosis in osimertinib-resistant cells. Moreover, co-treatment with bufalin and osimertinib restored the sensitivity of osimertinib-resistant cells to osimertinib-induced growth regression and apoptosis in vitro and in vivo. Mechanistically, MEK/ERK-dependent MCL-1 phosphorylation and Ku70-mediated MCL-1 overexpression confer osimertinib resistance in EGFR-mutant NSCLC cells. In osimertinib-resistant cells, bufalin modulates Ku70-mediated MCL-1 degradation, but not MEK/ERK/MCL-1 signaling. In conclusion, our study suggests that bufalin eliminates resistance to osimertinib by inhibiting Ku70-mediated MCL-1 overexpression, indicating that a combination of osimertinib and bufalin could be an effective additional treatment to overcome acquired resistance to osimertinib in NSCLC cells. • Ku70-mediated MCL-1 overexpression induced acquisition of osimertinib resistance in EGFR-mutant NSCLC cells. • Bufalin effectively reduced cell viability and induced apoptosis in osimertinib-resistant cells by suppressing Mcl-1. • Bufalin overcame acquired resistance to osimertinib by inhibiting Ku70-mediated MCL-1 overexpression. [ABSTRACT FROM AUTHOR]

Abstract In this paper, a new silicon-on-insulator superjunction lateral double-diffused MOSFET (SOI SJLDMOS) with a p-trench layer and stepped buried oxide, is investigated using 3D numerical simulation. The p-trench layer and stepped buried oxide distinguish it from a conventional SOI SJLDMOS. The etched buried oxide layer, with its stepped buried -oxide structure, which facilitates a more even electric field distribution via the electric field modulation effect, increases the breakdown-voltage (BV). Furthermore, the p-trench layer improves the doping concentration through compensation depletion, which further decreases the specific on-resistance (R on,sp). The simulation indicates that the new device has a higher BV (increased by 29%) than the conventional SOI SJLDMOS. At the same time, R on,sp decreases by 20% for the on-state for a given drift-region length. Highlights • A new SOI SJ LDMOS with p-trench and stepped buried oxide is proposed. • The p-trench layer for a higher doping concentration and lower on-resistance of the device. • The stepped buried oxide layer modulates the electric field distribution more uniform. • A 29% increase in the breakdown voltage for the SOI BSJ-PT LDMOS device. • A 20% decrease in the specific on-resistance for the SOI BSJ-PT LDMOS device. [ABSTRACT FROM AUTHOR]

For most of the commonly used DNA chips, the probes are usually single-stranded oligonucleotides and the targets are double-stranded DNAs (dsDNAs). Only one strand of the DNA serves as the target while the other competes with the probes immobilized on the chip for the target and therefore is regarded as the interfering strand. In this report, a novel technique was developed for improving the hybridization efficiency on DNA chips by using blocking oligos, which is complimentary to the target interfering strand to reduce the influence of the interfering strand. The hybridization efficiency of dsDNA was much lower than that of single-stranded DNA (ssDNA) when synthesized DNA targets were tested on the DNA chip. Blocking oligos can improve the hybridization efficiency of dsDNA to about 2/3 that of ssDNA. Blocking oligos have also been applied to PCR products of different lengths for hybridization. The hybridization efficiency with blocking oligos is about three times higher than that without blocking oligos. We have tested PCR products of 1054 and 435 bp using our blocking procedure, and the results are consistent. [Copyright &y& Elsevier]

Abstract Objective To explore the feasibility, safety and effectiveness of percutaneous cryoablation combined with systemic chemotherapy in the treatment of liver metastases from esophageal carcinoma (ECLM). Materials and methods We retrospectively collected data of 16 patients who received CT-guided percutaneous cryoablation concurrent systemic chemotherapy for liver metastases after primary esophageal carcinoma resection. Functional Assessment of Cancer Therapy-General (FACT-G) was used for the assessment of quality of life (QOL), and overall survival (OS), progression-free survival (PFS) and complications were also evaluated. Results The technical success rate was 96%, and no major complications related to cryoablation procedure were detected. Median OS and PFS after cryoablation were 14.5 months (range, 4–51 months) and 7.5 months (range, 1–31 months), respectively. The 1-year, 2-year, and 3-year survival rates were 56.3%, 31.3%, and 18.8%, respectively. The PFS rate at 6-month, 1-year, and 2-year after procedure were 68.8%, 31.3% and 18.8%, respectively. Furthermore, the QOL of patients was improved after cryoablation therapy compared with preoperative scores (P < 0.05). Conclusions Percutaneous cryoablation combined with systemic chemotherapy is a safe, feasible and effective method to treat liver metastases from esophageal carcinoma. And to a certain extent, this approach is very efficacious in improving the QOL of patients with ECLM. [ABSTRACT FROM AUTHOR]

In this paper, we propose a SiC LDMOS structure with a step compound drift region (SC-LDMOS). The proposed device has a compound drift region which consists of an n-type top layer, a step p-type middle layer and an n-type bottom layer. The step p-type middle layer can introduce two new electric field peaks and uniform the distribution of the electric field in the n-type top layer, which can modulate the surface electric field and improve the breakdown voltage of the proposed structure. In addition, the n-type bottom layer is applied under the heavy doping p-type middle layer，which contributes to realize the charge balance. Furthermore, it can also increase the doping concentration of the n-type top layer, which can decrease the on resistance of the proposed device. As a simulated result, the proposed device obtain a high BV of 976 V and a low R sp,on of 7.74 mΩ·cm 2 . Compared with the conventional single REUSRF LDMOS and triple RESURF LDMOS, BV of proposed device is enhanced by 42.5% and 14.7%, respectively and R sp,on is reduced by 37.3% and 30.9%, respectively. Meanwhile, the switching delays of the proposed device are significantly shorter than the conventional triple RESURF LDMOS. [ABSTRACT FROM AUTHOR]

In this paper, a new structure for GaN MISFET is proposed to enhance its breakdown voltage. The proposed structure uses an Aluminum nitride (AlN) buried layer embedded inside the GaN buffer layer. The AlN buried layer is employed to reduce the peak electric field strength near the gate, introducing a high electric field peak in the GaN buffer layer. The GaN/AlN heterojunction formed by the GaN buffer layer and the AlN buried layer introduces two electric field peaks, and enhances the uniformity of the electric field distribution in the GaN buffer layer. Simulation results of the proposed structure show that the breakdown voltage is enhanced by 78% when compared to the conventional GaN MISFET. Moreover, the specific on-resistance ( R on,sp ) is improved since the AlN buried layer provides two-dimensional electron gases in the GaN buffer which can cause the charge to increase. [ABSTRACT FROM AUTHOR]

In this paper, the performance of graded channel double-gate MOSFET (GC-DGFET) that utilizes the charge-plasma concept and a high-κ spacer is investigated through 2-D device simulations. The results demonstrate that GC-DGFET with high-κ spacer can effectively improve the ON-state driving current ( I ON ) and reduce the OFF-leakage current ( I OFF ). We find that reduction of the initial energy barrier between the source and channel is the origin of this I ON enhancement. The reason for the I OFF reduction is identified to be the extension of the effective channel length owing to the fringing field via high-κ spacers. Consequently, these devices offer enhanced performance by reducing the total gate-to-gate capacitance ( C gg ) and decreasing the intrinsic delay (τ). [ABSTRACT FROM AUTHOR]

This paper presents a breakdown-enhanced AlGaN/GaN MISFET with a source-connected P-buried layer combined with field plates (SC-PBL FPs MISFET). A TCAD tool was used to analyze the breakdown characteristics of the proposed structure, and results show that in comparison to the conventional gate field plate MISFET (GFP-C MISFET), the proposed structure provides a significant increase of breakdown voltage ( V BK ) due to redistribution of electric field in the gate-drain region induced by the SC-PBL and the FPs. The optimized SC-PBL FPs MISFET with a gate-drain spacing of 6 μm achieved a high Baliga’s figure of merit of 2.6 GW cm −2 with a corresponding breakdown voltage ( V BK ) of 1311.62 V and specific on resistance ( R ON,sp ) of 0.66 mΩ cm 2 , which demonstrates a good trade-off between R ON,sp and V BK compared to the GFP-C MISFET with V BK of 524.27 V and R ON,sp of 0.61 mΩ cm 2 . [ABSTRACT FROM AUTHOR]

A silicon-on-insulator (SOI) lateral double-diffused MOSFET (LDMOSFET) with a buried field plate (BFP-LDMOS) is proposed. Its characteristics are studied using 2-D simulations. The proposed structure features double buried field plates which are surrounded by buried oxide (BOX) and connected to the source and drain electrode, respectively. The drain buried field plate (DBFP) prevents a premature breakdown at the interface of the silicon/BOX and enhances the dielectric field. The source buried field plate (SBFP) introduces a new electric-field peak and modulates the distribution of the horizontal electric field. In addition, the BFPs replace part of the BOX, which is useful to minimize self-heating effects (SHE). According to the simulation results, compared to a conventional SOI LDMOS (C-LDMOS), the breakdown voltage (BV) in the BFP-LDMOS increases from 128 V to 182 V. The specific on-state resistance ( R on,sp ), however, decreases from 20.46 mΩ cm 2 to 18.50 mΩ cm 2 . Moreover, the maximum lattice temperature at 1 mW/μm and V gs = 10 V is reduced by 33.8 K compared to the C-LDMOS device. [ABSTRACT FROM AUTHOR]

Major histocompatibility class II (MHC II)-specific activation of CD4 + T helper cells generates specific and persistent adaptive immunity against tumors. Emerging evidence demonstrates that MHC II is also involved in basic pain perception; however, little is known regarding its role in the development of cancer-induced bone pain (CIBP). In this study, we demonstrate that MHC II expression was markedly induced on the spinal microglia of CIBP rats in response to STAT1 phosphorylation. Mechanical allodynia was ameliorated by either pharmacological or genetic inhibition of MHC II upregulation, which was also attenuated by the inhibition of pSTAT1 and pERK but was deteriorated by intrathecal injection of IFNγ. Furthermore, inhibition of ERK signaling decreased the phosphorylation of STAT1, as well as the production of MHC II in vivo and in vitro . These findings suggest that STAT1 contributes to bone cancer pain as a downstream mediator of ERK signaling by regulating MHC II expression in spinal microglia. [ABSTRACT FROM AUTHOR]

Cancer induced bone pain (CIBP) remains one of the most intractable clinical problems due to poor understanding of its underlying mechanisms. Recent studies demonstrate the decline of inhibitory interneurons, especially GABAergic interneurons in the spinal cord, can evoke generation of chronic pain. It has also been reported that neuronal MHC-I expression renders neurons vulnerable to cytotoxic CD8 + T cells and finally lead to neurons apoptosis in a variety neurological disorders. However, whether MHC-I could induce the apoptosis of GABAergic interneurons in spinal cord and contribute to the development of CIBP remains unknown. In this study, we investigated roles of MHC-I and underlying mechanisms in CIBP on a rat model. Our results showed that increased MHC-I expression on GABAergic interneurons could deplete GABAergic interneurons by inducing their apoptosis in the spinal dorsal horn of tumor-bearing rats. Pretreatment of MHC-I RNAi-lentivirus could prevent the apoptosis of GABAergic interneurons and therefore alleviated mechanical allodynia induced by tumor cells intratibial injection. Additionally, we also found that CD8 + T cells were colocalized with MHC-I and GABAergic neurons and presented a significant and persistent increase in the spinal cord of tumor-bearing rats. Taken together, these findings indicated that MHC-I could evoke CIBP by promoting apoptosis of GABAergic interneurons in the dorsal horn, and this apoptosis was closely related to local CD8 + T cells. [ABSTRACT FROM AUTHOR]

In this work, we propose a junctionless MOSFET with asymmetric gates (AG-JL MOSFET). This device is a double gate structure with a lateral offset between the gate, and this leads to different characteristic than a conventional double gate structure. Specifically, the asymmetric gate modulates the effective channel length depending on whether the device is in the ON or OFF state, which this leads to more ideal device characteristics. A comprehensive device performance comparison including the I ON /I OFF ratio, subthreshold slope (SS), and drain-induced barrier lowering (DIBL) between the proposed device and a conventional device is presented. The proposed device exhibits superior performance when compared a conventional device, and results show that it is also less sensitive to process variations. [ABSTRACT FROM AUTHOR]

In this work, a sandwich vertical tunnel field effect transistor (SDG-VTFET) is presented and studied. Since the dominant carrier tunneling of SDG-VFET occurs in a direction that is in line with the gate field, high ON-state current and steep subthreshold slope are observed. Comparisons between SDG-VFET and double gate tunnel field effect transistor are made to clarify advantages of SDG-VTFET. The simulation results of our work show that SDG-VTFET has stronger gate control, steeper subthreshold slope and higher ON-state current. The device plays a promising candidate for future low power circuit applications. [ABSTRACT FROM AUTHOR]

In this work, we propose and simulate an asymmetric dual-gate tunneling FET (ADG-TFET) combining a tunneling field effect transistor (TFET) with a junctionless field effect transistor (JLFET). The current is controlled by an in the bottom channel potential barrier as well as the reverse-biased P+ pocket-Intrinsic region (p-i) tunnel junction bandgap, which combines the merits of both bandgap-controlled TFET and barrier-controlled JLFET. The simulation results of ADG-TFET with high-κ dielectric material (HfO 2 ) of 40-nm gate length show excellent characteristics with high I ON /I OFF ratio of 3.3 × 10 10 and I ON of 302 μA/μm, a steep subthreshold slope (SS) for point SS of 35 mV/decade and average SS of 54 mV/decade at room temperature, which indicates that ADG-TFET is a promising candidate for future low power circuit applications. [ABSTRACT FROM AUTHOR]

Previously, we showed that activation of the spinal CXCL9, 10/CXCR3 pathway mediated bone cancer pain (BCP) in rats. However, the cellular mechanism involved is poorly understood. Here, we found that the activated CXCR3 was co-localized with either neurons, microglia, and astrocytes in the spinal cord, or non-peptidergic-, peptidergic-, and A-type neurons in the dorsal root ganglion. The inoculation of Walker-256 mammary gland carcinoma cells into the rat’s tibia induced a time-dependent phosphorylation of Akt and extracellular signal-regulated kinase (ERK1/2) in the spinal cord, and CXCR3 was necessary for the phosphorylation of Akt and ERK 1/2. Meanwhile, CXCR3 was co-localized with either pAkt or pERK1/2. Blockage of either Akt or ERK1/2 prevented or reversed the mechanical allodynia in BCP rats. Furthermore, there was cross-activation between PI3K/Akt and Raf/MEK/ERK pathway under the BCP condition. Our results demonstrated that the activation of spinal chemokine receptor CXCR3 mediated BCP through Akt and ERK 1/2 kinase, and also indicated a crosstalk between PI3K/Akt and Raf/MEK/ERK signaling pathways under the BCP condition. [ABSTRACT FROM AUTHOR]

This study intends to conquer the mystery of microRNA-16-5p/erythropoietin-producing hepatocellular A1/nuclear factor-κB signaling (miR-16-5p/EPHA1/NF-κB signaling) in breast cancer. Expression of miR-16-5p, EPHA1 and NF-κB signaling-related proteins were detected. Gene overexpression or silencing was used to examine the biological roles of bone marrow mesenchymal stem cells (BMSCs)-derived exo -miR-16-5p in breast cancer. The effect of exo-miR-16-5p on tumorigenesis of breast cancer was confirmed by the xenograft nude mouse model. Low miR-16-5p and high EPHA1 expression were examined in breast cancer. BMSCs-derived exosomes, up-regulated miR-16-5p or down-regulated EPHA1 restrained epithelial-mesenchymal transition (EMT) of breast cancer cells and tumor growth in nude mice. Down-regulated miR-16-5p or up-regulated EPHA1 activated NF-κB signaling. Knockdown of EPHA1 or inhibition of NF-κB signaling reversed the effects of down-regulated miR-16-5p on breast cancer cells. BMSCs-derived exosomal miR-16-5p hinders breast cancer cells progression via EPHA1/NF-κB signaling axis. • Low miR-16-5p and high EPHA1 expression present in breast cancer. • BMSCs-derived exosomes deliver miR-16-5p to inhibit EMT in breast cancer. • MiR-16-5p targets EPHA1. • Down-regulated miR-16-5p or up-regulated EPHA1 activated NF-κB signaling. • Knockdown of EPHA1 or inhibition of NF-κB signaling reversed the effects of down-regulated miR-16-5p on breast cancer cell. [ABSTRACT FROM AUTHOR]

Three pairs of undescribed enantiomeric α -pyrone derivatives (1a / 1b – 3a / 3b) and six previously undescribed congeners (4 – 9), were obtained from the fungus Alternaria brassicicola , which was isolated from the fresh leaves of Siegesbeckia pubescens Makino (Compositae). The structures of these new compounds were identified by extensive NMR spectroscopic and HRESIMS data, and their absolute configurations were further elucidated by ECD calculations, a modified Mosher's method, and single-crystal X-ray diffraction. This is the first report of three pairs of enantiomeric α -pyrone derivatives from fungus Alternaria brassicicola , and these enantiomers were successfully acquired from scalemic mixtures via chiral HPLC. Compounds 1a/1b – 3a/3b and 4 – 9 were evaluated for the herbicidal activity against Echinochloa crusgalli , Setaria viridis , Portulaca oleracea and Taraxacum mongolicum. At a concentration of 100 μ g/mL, compounds 1a and 1b could significantly inhibit the germination of the monocotyledon weed seeds (E. crusgalli and S. viridis) with inhibitory ratios ranging from 68.6 ± 6.4% to 84.2 ± 5.1%, , which was equivalent to that of the positive control (glyphosate). In addition, the structure-herbicidal activity relationship of the above compounds was discussed. To a certain extent, the results of this study will attract great interest for the potential practical application of promising fungal metabolites, α -pyrone derivatives, as ecofriendly herbicides. [Display omitted] • Twelve new bioactive metabolites were isolated from the fungus Alternaria brassicicola. • Their absolute configurations were characterized by a modified Mosher's method, chemical conversion, X-ray crystallography analysis, and ECD calculations. • Compounds 1a / 1b – 3a / 3b are the first examples of enantiomeric α -pyrone derivatives from the fungus A. brassicicola. • Compounds 1a and 1b could significantly inhibit the germination of the monocotyledon weed seeds (E. crusgalli and S. viridis), which was equivalent to that of the positive control (glyphosate). Three pairs of undescribed enantiomeric α -pyrone derivatives (1a / 1b – 3a / 3b) and six undescribed congeners (4 – 9), were obtained from the fungus Alternaria brassicicola that was isolated from the fresh leaves of Siegesbeckia pubescens Makino (Compositae). The structures of these new compounds were characterized by extensive NMR spectroscopic and HRESIMS data, and their absolute configurations were further elucidated by a modified Mosher's method, chemical conversion, single-crystal X-ray diffraction analysis, and ECD calculations. This is the first report of three pairs of enantiomeric α -pyrone derivatives from the fungus A. brassicicola , and these enantiomers were successfully acquired from scalemic mixtures via chiral HPLC. Compounds 1a/1b – 3a/3b and 4 – 9 were evaluated for the herbicidal activity against Echinochloa crusgalli , Setaria viridis , Portulaca oleracea , and Taraxacum mongolicum. At a concentration of 100 μ g/mL, compounds 1a and 1b could significantly inhibit the germination of monocotyledon weed seeds (E. crusgalli and S. viridis) with inhibitory ratios ranging from 68.6 ± 6.4% to 84.2 ± 5.1%, which was equivalent to that of the positive control (glyphosate). The potential structure-herbicidal activity relationship of these compounds was also discussed. To a certain extent, the results of this study will attract great interest for the potential practical application of promising fungal metabolites, α -pyrone derivatives, as ecofriendly herbicides. [ABSTRACT FROM AUTHOR]

[Display omitted] • Seven new secondary metabolites and two known analogues were isolated from Daldinia sp. TJ403-LS1. • Their structures were elucidated via extensive spectroscopic analyses and ECD calculations. • Compound 1 showed potent immunosuppressive activity. • Compounds 1 , 6 , 8 , and 9 showed significant BChE inhibitory activity. Five new acetylenic phenol derivatives (1 – 4 and 7), one new benzofuran derivative (8), one new naphthol derivative (9), and two known analogues (5 and 6), were isolated and identified from an endophytic fungus Daldinia sp. TJ403-LS1 that was isolated from the medicinally valuable plant Anoectochilus roxburghii. Their structures were elucidated by means of extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. In addition, compound 1 exhibited remarkable immunosuppressive activity against LPS and anti-CD3/anti-CD28 mAbs activated murine splenocytes proliferation with the same IC 50 values of 0.06 μM and BChE inhibitory activity with an IC 50 value of 6.93 ± 0.71 μM, and compounds 6 , 8 and 9 showed excellent BChE inhibitory activity with IC 50 values of 16.00 ± 0.30, 23.33 ± 0.55, and 15.53 ± 0.39 μM, respectively (positive drug neostigmine, IC 50 = 49.60 ± 6.10 μM), highlighting the promising potentials to be designed and developed as immunosuppressive and BChE inhibitory agents. [ABSTRACT FROM AUTHOR]

Cancer-induced bone pain (CIBP) remains a major challenge in patients suffering from bone metastases because of the complex mechanisms and unsatisfactory treatments. Emerging evidence have shown that activation of inflammasomes contribute to the development of inflammatory and neuropathic pain. However, the role of spinal inflammasomes in CIBP remains unclear. In the present study, we explored the specific cellular mechanisms of NLRP3 inflammasome in the process of CIBP in rats. MCC950 is a small molecule inhibitor of the NLRP3 inflammasome that exhibits remarkable activity in inflammatory diseases. Our behavioral results confirmed that both single and persistent treatment with MCC950 markedly attenuated CIBP-related mechanical allodynia. The expression of NLRP3 inflammasome, including NLRP3, ASC, Caspase-1, were significantly increased in a time-dependent manner. Furthermore, spinal IL-1β, cleaved by cysteine-aspartic acid protease, was upregulated in this study. Chronic administration with MCC950 restored the protein expression of NLRP3 inflammasome and significantly suppressed the upregulation of IL-1β. Spinal NLRP3 inflammasome might be a novel therapeutic target for treatment of CIBP. [ABSTRACT FROM AUTHOR]