Selenium dioxide promoted selenylation/cyclization of leucosceptrane sesterterpenoids.

A novel selenium dioxide promoted selenylation/cyclization of leucosceptrane sesterterpenoids was reported. Two types of leucosceptrane derivatives with different valence states of selenium atoms (Se2+ and Se4+) were obtained. The mechanisms of these two processes were proposed, and the selenium-containing derivates may serve as intermediates of Riley oxidation that could be trapped with appropriate substrates. Immunosuppressive activity screening revealed that 10 and 11 had obvious inhibitory effects on IFN-γ production, with IC50 values of 5.29 and 17.60 µM, respectively, which were more active than their precursor leucosceptroid A.

Leucosceptrane sesterterpenoids from Tibetan Leucosceptrum canum and their immunosuppressive activity.

Phytochemical investigation on the leaves of Tibetan Leucosceptrum canum, a Chinese medicinal herb, led to the isolation of seven new leucosceptrane sesterterpenoids (1-7) and five known analogs (8-12). Comprehensive spectroscopic analysis (including 1D and 2D NMR, and HRMS), quantum chemistry computations, and single crystal X-ray crystallographic analysis were applied to elucidate their structures. Compounds 1-3 and 6 were the first examples of the leucosceptrane sesterterpenoids with rare C-2 oxidation. Compound 2 exhibited immunosuppressive activities via suppressing the secretion of cytokines IL-6 and TNF-α in LPS-induced macrophages RAW264.7 with IC50 values of 13.39 and 19.34 µM, respectively.

TCF12 induces ferroptosis by suppressing OTUB1-mediated SLC7A11 deubiquitination to promote cisplatin sensitivity in oral squamous cell carcinoma.

Chemotherapy resistance is a major obstacle to effective cancer treatment, and promotion of ferroptosis can suppress cisplatin resistance in tumor cells. TCF12 plays a suppressive role in oral squamous cell carcinoma (OSCC), but whether it participates in the regulation of cisplatin resistance by modulating ferroptosis remains unclear. Here, we found that TCF12 expression was decreased in OSCC cells compared with normal oral cells, and it was reduced in cisplatin (DDP)-resistant OSCC cells compared with parental cells. Moreover, overexpression of TCF12 sensitized DDP-resistant cells to DDP by promoting ferroptosis. Intriguingly, silencing TCF12 reversed the promotion effect of the ferroptosis activator RSL3 on ferroptosis and DDP sensitivity, and overexpressing TCF12 antagonized the effect of the ferroptosis inhibitor liproxstatin-1 on ferroptosis and DDP resistance. Mechanically, TCF12 promoted ubiquitination of SLC7A11 and decreased SLC7A11 protein stability through transcriptional repression of OTUB1, thereby facilitating ferroptosis. Consistently, SLC7A11 overexpression neutralized the promotion effect of TCF12 on ferroptosis and DDP sensitivity. Additionally, upregulation of TCF12 hindered the growth of mouse OSCC xenografts and enhanced the DDP sensitivity of xenografts by inducing ferroptosis. In conclusion, TCF12 enhanced DDP sensitivity in OSCC cells by promoting ferroptosis, which was achieved through modulating SLC7A11 expression via transcriptional regulation of OTUB1.

Frass deposition from pest outbreaks affects soil organic carbon and its relationship with environmental factors in a deciduous broad-leaved forest.

Forest defoliators are one of the major biological disturbances to forest ecosystems. As one of the abnormal nutrient input paths into forest ecosystems, frass deposition from the pest outbreak plays a critical role in regulating soil organic carbon (SOC) in forest ecosystems. However, how frass deposition affects SOC and its fractions in forests remains unclear. Based on a severe outbreak of defoliator in an oak-sweetgum mixed forest in Jigong Mountain in 2014, we compared the difference in SOC between plots with and without frass deposition for 4 consecutive years. The results showed that frass deposition led to a significant increase of 25.1 % in soil microbial biomass C (MBC) and 32.0 % in dissolved organic C (DOC) in 2014, which further escalated to 50.4 % and 50.6 % in the subsequent year (2015), respectively. The response of SOC to frass deposition lagged behind MBC and DOC. Specifically, there was no change in SOC in 2014, but a significant increase (50.9 %) was observed in the subsequent 2-3 years. The positive dependences of MBC and DOC upon fine root biomass were negated under frass deposition, while the relationship between SOC and fine root biomass remained unaffected. Soil organic carbon and DOC showed non-linear responses to frass amount and the changed soil nitrogen content. Our finding that the response of SOC to frass deposition lagged behind soil labile C indicates that SOC exhibits a certain resilience towards forest disturbance. The findings also imply that investigating the long-term impacts of frass deposition on SOC in forests would contribute to the scientific assessment of forest C cycling under disturbance.

Co-Assembly of Polyoxometalates and Porphyrins as Anode for High-Performance Lithium-Ion Batteries.

Polyoxometalates (POMs) have been considered one of the most promising anode candidates for lithium-ion batteries (LIBs) in virtue of their high theoretical capacity and reversible multielectron redox properties. However, the poor intrinsic electronic conductivity, low specific surface area, and high solubility in organic electrolytes hinder their widespread applications in LIBs. Herein, a novel hybrid nanomaterial is synthesized by co-assembling POMs and porphyrins (PMo12/CoTPyP) through a facile solvothermal method. The POM clusters are stabilized by porphyrin units through electrostatic interactions, which simultaneously realize the uniform dispersion of POMs and porphyrin units. Benefiting from the generated sub-1 nm channels for fast ion transport and the synergistic effect between evenly distributed PMo12 clusters and high-conductive CoTPyP units, the LIB based on the optimized PMo12/CoTPyP anode exhibits significantly improved Li+ storage capability as well as superior rate and cycling performance. The results of density functional theory simulations further reveal that the co-assembly of PMo12 and CoTPyP can accelerate the mobility of Li+ and electrons, which in turn promotes the enhancement of LIBs performance. This work paves a strategy for synthesizing POMs-based anode materials with simultaneously high dispersibility, redox activity, and stability.

Immunosuppressive leucosesterterpane and penta-nor-leucosesterterpane sesterterpenoids from Leucosceptrum canum.

Five undescribed leucosesterterpane sesterterpenoids, leucosceptrines A-E, two undescribed penta-nor-leucosesterterpane (C20) sesterterpenoids, nor-leucosceptrines A and B, and three known analogues, were obtained from the aerial parts of Leucosceptrum canum of Chinese origin. Leucosceptrines A-C are the first examples of leucosesterterpane-type sesterterpenoids with unclosed dihydropyran rings and reverse configurations at chiral centers C-4 and/or C-12. Nor-leucosceptrines A and B possesses an unusual penta-nor-leucosesterterpane skeleton. Their structures were unambiguously elucidated through comprehensive spectroscopic analyses and single-crystal X-ray diffraction. A plausible biogenetic pathway for these sesterterpenoids was proposed. The immunosuppressive effects of these isolates on the secretion of the cytokine IFN-γ by T cells stimulated with anti-CD3/CD28 monoclonal antibodies were observed with different potencies.

Unusual immunosuppressive pyridine-containing bisnor- (c23), tetranor- (c21) and pentanor- (c20) sesterterpenoids from Tibetan Leucosceptrum canum.

An unusual pyridine-containing sesterterpenoid, leucosceptrodine (1), and five new nor-leucosceptrane sesterterpenoids, including bisnor- (C23, 2), tetranor- (C21, 3) and pentanor- (C20, 4-6) skeletons, were isolated from the leaves of Tibetan Leucosceptrum canum. Their structures including their absolute configurations were determined by extensive spectroscopic analyses and quantum chemical calculations. A single crystal of one epimer (5) was crystallized from a pair of inseparable epimers, and its structure including its absolute configuration was determined by X-ray crystallographic analysis. The immunosuppressive activities of compounds 1-4 with different potencies were evaluated by inhibiting the secretion of cytokines TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.

Insecticide Susceptibility and KDR Mutations in Aedes Albopictus Collected from Seven Districts of Guangyuan city, Northern Sichuan, China.

The Asian tiger mosquito, Aedes albopictus, is an important vector of chikungunya, dengue, yellow fever, and Zika viruses. Vector control remains an important means for the prevention and control of vector-borne diseases. The development of insecticide resistance has become a serious threat to the efficacy of insecticide-based control programs. To understand the resistance status and the underlying genetic mechanism in mosquitoes in Guangyuan City of Sichuan Province, China, we investigated the susceptibility of Ae. albopictus to four commonly used insecticides. We found that all the examined populations were susceptible to malathion and propoxur. However, Ae. albopictus populations in Guangyuan showed a possible resistance to the two tested pyrethroids (beta-cypermethrin and deltamethrin). Notably, phenotypic resistance to deltamethrin was detected in 2 of the 7 populations. The potential of resistance to pyrethroids was confirmed by the presence of knockdown resistance (kdr) related mutations in the voltage-gated sodium channel. Four kdr mutations (V1016G, I1532T, F1534L, and F1534S) were identified to be present alone or in combination, and their distribution displayed significant spatial heterogeneity. These findings are helpful for making evidence-based mosquito control strategies and highlight the need to regularly monitor the dynamics of pyrethroid resistance in this city.

Leucosceptrane Sesterterpenoids as a New Type of Natural Immunosuppressive Agents in Treating Sepsis.

Intragastric administration of the total sesterterpenoid extract (TSE) of medicinal plant Leucosceptrum canum at 2.5 g/kg dose protected mice from LPS-induced sepsis. Phytochemical investigation led to the isolation and identification of 47 leucosceptrane sesterterpenoids (1-47) including 30 new compounds (1-30) with complicated oxygenation patterns. Biological screening indicated their immunosuppressive activity via inhibiting IFN-γ secretion and/or proliferation of T cells with different potencies. Mechanism study of compounds 9, 25, and 32 revealed that they inhibited the activations of AKT-mTOR, JNK, p38 MAPK or ERK pathway in T cells and macrophages. In addition, compounds 9 and 25 induced G0/G1 cell arrest of T cells. The major component, leucosceptroid N (32), significantly lowered the levels of IL-6 and TNF-α in peripheral blood serum, and ameliorated the multiorgan damages of LPS-induced sepsis mice at 25 mg/kg dose. These findings suggest that leucosceptrane sesterterpenoids are a new type of potential immunosuppressive agents for sepsis treatment.

Discovery of Unusual Sesterterpenoids from Colquhounia coccinea var. mollis and Their Metabolic Implications.

Three unusual sesterterpenoids featuring unprecedented rearranged colquhounane (C25) and tetranorcolquhounane (C21) frameworks, colquhounoids E (1) and F (3) and norcolquhounoid F (2), were isolated from a Lamiaceae medicinal plant Colquhounia coccinea var. mollis. Their structures were elucidated by spectroscopic analysis and quantum chemical calculations. A biomimetic inspired regioselective cyclopropane cleavage was achieved under acidic conditions. The immunosuppressive activities of these new sesterterpenoids were also evaluated.

Litter inputs exert greater influence over soil respiration and its temperature sensitivity than roots in a coniferous forest in north-south transition zone.

The changes in carbon inputs of litter and roots to forest soils caused by climate change will result in a serious cascade effect on soil respiration and its temperature sensitivity (Q10). To differentiate and quantify the effects of surface litter and living roots on soil respiration and Q10, and further explore the role of abiotic factors and microbial properties on soil respiration and Q10, a short-term (two years) detritus input and removal treatment experiment was conducted in a coniferous forest of central China. Soil temperature, soil moisture, C/N, microbial biomass and community composition were analyzed to explore the drive mechanisms of soil respiration and Q10 in response to carbon inputs. The results showed that litter addition increased soil respiration by 22 %, while litter or roots removal did not affect soil respiration, which might be ascribed to the "priming effects" mediated by fresh plant litter. We also found that litter addition increased Q10, while litter removal decreased Q10. Litter addition significantly enhanced the microbial biomass for any single functional group and altered soil microbial community composition. Structural equation model further proved that microbial biomass and community composition exerted stronger impacts on Q10 than do soil abiotic factors. Soil moisture, microbial biomass and community structure were main factors in predicting soil respiration. The study highlights the important role of litter inputs compared with living roots in carbon cycling in short-term and deepens our understanding on the complex relationships among soil respiration, soil micro-environment and microbial community composition.

A new sesquiterpene synthase catalyzing the formation of (R)-ß-bisabolene from medicinal plant Colquhounia coccinea var. mollis and its anti-adipogenic and antibacterial activities.

The sesquiterpene ß-bisabolene possessing R and S configurations is commonly found in plant essential oils with antimicrobial and antioxidant activities. Here, we report the cloning and functional characterization of a (R)-ß-bisabolene synthase gene (CcTPS2) from a Lamiaceae medicinal plant Colquhounia coccinea var. mollis. The biochemical function of CcTPS2 catalyzing the cyclization of farnesyl diphosphate to form a single product (R)-ß-bisabolene was characterized through an engineered Escherichia coli producing diverse polyprenyl diphosphate precursors and in vitro enzyme assay, indicating that CcTPS2 was a high-fidelity (R)-ß-bisabolene synthase. The production of (R)-ß-bisabolene in an engineered E. coli strain harboring the exogenous mevalonate pathway, farnesyl diphosphate synthase and CcTPS1 genes was 17 mg/L under shaking flask conditions. Ultimately, 120 mg of purified (R)-ß-bisabolene was obtained from the engineered E. coli, and its structure was elucidated by detailed spectroscopic analyses (including 1D and 2D NMR, and specific rotation). Four chimeric enzymes were constructed through domain swapping, which altered the product outcome, indicating the region important for substrate and product specificity. In addition, (R)-ß-bisabolene exhibited anti-adipogenic activity in the model organism Caenorhabditis elegans and antibacterial activity selectively against Gram-positive bacteria.

Synergistic effect of nano zinc oxide and tea tree essential oil on the properties of soluble soybean polysaccharide films.

Soluble soybean polysaccharide (SSPS)-based composite films with the addition of nano zinc oxide (nZnO, 5 wt% based on SSPS) and tea tree essential oil (TTEO, 10 wt% based on SSPS) were developed by the casting method. The effect of the combination of nZnO and TTEO on the microstructure and physical, mechanical and functional properties of SSPS films was evaluated. The results showed that the SSPS/TTEO/nZnO film exhibited enhanced water vapor barrier properties, thermal stability, water resistance, surface wettability, and total color difference, and almost completely prevented ultraviolet light transmission. The addition of TTEO and nZnO had no significant effect on the tensile strength and elongation at break of the films, but decreased the percentage of light transmittance of the films at 600 nm from 85.5 % to 10.1 %. The DPPH radical scavenging activity of the films significantly increased from 46.8 % (SSPS) to 67.7 % (SSPS/TTEO/nZnO) due to the presence of TTEO. Scanning electron microscopy analysis indicated that nZnO and TTEO were evenly dispersed in the SSPS matrix. The synergistic effect of nZnO and TTEO endowed the SSPS film with excellent antibacterial activity against E. coli and S. aureus, suggesting that the SSPS/TTEO/nZnO film could be a promising material for active packaging applications.

Secoiridoids from the traditional Chinese medicine Swertia pseudochinensis.

Detailed phytochemical investigation on the traditional Chinese medicine Swertia pseudochinensis Hara led to the isolation of ten undescribed secoiridoids and fifteen known analogs. Their structures were elucidated by extensive spectroscopic analysis (including 1D and 2D NMR, and HRESIMS). Selected isolates were assayed for their anti-inflammatory and antibacterial activities, and moderate anti-inflammatory activity via inhibiting the secretion of cytokines IL-6 and TNF-α in macrophages RAW264.7 induced by LPS were observed. Antibacterial activity against Staphylococcus aureus was not found at 100 µM.

INDETERMINATE1 autonomously regulates phosphate homeostasis upstream of the miR399-ZmPHO2 signaling module in maize.

The macronutrient phosphorus is essential for plant growth and development. Plants have evolved multiple strategies to increase the efficiency of phosphate (Pi) acquisition to protect themselves from Pi starvation. However, the crosstalk between Pi homeostasis and plant development remains to be explored. Here, we report that overexpressing microRNA399 (miR399) in maize (Zea mays) is associated with premature senescence after pollination. Knockout of ZmPHO2 (Phosphate 2), a miR399 target, resulted in a similar premature senescence phenotype. Strikingly, we discovered that INDETERMINATE1 (ID1), a floral transition regulator, inhibits the transcription of ZmMIR399 genes by directly binding to their promoters, alleviating the repression of ZmPHO2 by miR399 and ultimately contributing to the maintenance of Pi homeostasis in maize. Unlike ZmMIR399 genes, whose expression is induced by Pi deficiency, ID1 expression was independent of the external inorganic orthophosphate status, indicating that ID1 is an autonomous regulator of Pi homeostasis. Furthermore, we show that ZmPHO2 was under selection during maize domestication and cultivation, resulting in a more sensitive response to Pi starvation in temperate maize than in tropical maize. Our study reveals a direct functional link between Pi-deprivation sensing by the miR399-ZmPHO2 regulatory module and plant developmental regulation by ID1.

Preparation of Bismuth Tungstate/Preoxidized Acrylonitrile/Acrylic Acid Copolymer Composite Nanofiber Membrane and Its Photocatalytic Properties.

BACKGROUND: In this patent article, a novel bismuth tungstate/preoxidized acrylonitrile/ acrylic acid (AN/AA) copolymer composite nanofiber membrane was prepared, which was used as the visible light catalyst. METHODS: AN/AA copolymer was synthesized, which was electrospun with bismuth nitrate and sodium tungstate to prepare the composite nanofiber. Then the composite nanofiber was preoxidized to prepare the bismuth tungstate/preoxidized AN/AA composite nanofiber membrane containing adsorption moiety and photocatalytic active moiety. RESULTS: The photocatalytic activity of bismuth tungstate/preoxidized AN/AA composite nanofiber membrane with different preoxidized temperature, heating rate, and holding time by catalytic degradation of methylene blue was investigated. The optimal preoxidized conditions were as follows: the preoxidized temperature was heated to 200 °C with the heating rate of 1°C/min and the holding time at this temperature was 12 h. The chemical structure and morphology of the composite nanofiber membrane were characterized by FTIR, XRD, and SEM. CONCLUSION: The bismuth tungstate/preoxidized AN/AA composite nanofiber membrane obtained good photocatalytic properties and reusability under visible light. The degradation rate of methylene blue by this visible light catalyst could reach 90.24% for 4.5 h, and the degradation rate remained 81.53% for 4.5 h after 5 reuses.

Secondary metabolites from the Mongolian medicine Lomatogonium carinthiacum.

Systematic phytochemical investigation on the Mongolian medicinal herb Lomatogonium carinthiacum led to the isolation of 12 monoterpenoids including three new secoiridoids (1, 2 and 4) and one new iridoid glycoside (13), one new monoterpenoid alkaloid (3), and three new sesquiterpenoids (14-16). Comprehensive spectroscopic analysis (including 1D and 2D NMR, and HRESIMS) and quantum chemistry computations (including ECD and NMR calculations) were applied to elucidate their structures. Weak immunosuppressive activities were observed for the new isolates via inhibiting T cell proliferation and cytokine IFN-γ secretion in vitro.

CREB1 Facilitates GABAergic Neural Differentiation of Human Mesenchymal Stem Cells through BRN2 for Pain Alleviation and Locomotion Recovery after Spinal Cord Injury.

The transplantation of GABAergic neuron cells has been reported to alleviate nerve pain and improve motor function after spinal cord injury (SCI). However, human mesenchymal stem cell (hMSC) differentiation into GABAergic neuron cells in a sufficient quantity remains to be accomplished. From a database screening, cAMP-responsive element-binding protein 1 (CREB1) was chosen as a potential modulator due to its critical role in the protein-protein interaction of genes related to GABAergic neural differentiation. Here, CREB1 was overexpressed in transfected hMSCs, where CREB1 could induce differentiation into GABAergic neuron cells with an upregulation of Map2 and GAD1 by 2- and 3.4-fold, respectively. Additionally, GABAergic neural differentiation was enhanced, while Notch signaling was inhibited, and BRN2 transcriptional activation played an important role in neuronal maturation. Moreover, transfected hMSCs injected into immunocompromised mice caused by CsA exhibited the neuronal markers Tuj1 and Map2 via the intraspinal route, suggesting an improvement in survival and neural differentiation. Significantly, improvement in both BMS scores (6.2 ± 1.30 vs. 4 ± 0) and thermal hyperalgesia latency (7.74 ± 2.36 s vs. 4.52 ± 0.39 s) was seen compared with the SCI naïve treatment at 4 weeks post-transplantation. Our study demonstrates that CREB1 is crucial in generating induced GABAergic neuron cells (iGNs) originating from hMSCs. Transplanting iGNs to injured spinal cord provides a promising strategy for alleviating neuropathic pain and locomotion recovery after SCI.

Effects of Different Radiation Sources on the Performance of Collagen-Based Corneal Repair Materials and Macrophage Polarization.

Owing to the lack of donor corneas, there is an urgent need for suitable corneal substitutes. As the main component of the corneal stroma, collagen has great advantages as a corneal repair material. If there are microorganisms such as bacteria in the corneal repair material, it may induce postoperative infection, causing the failure of corneal transplantation. Therefore, irradiation, as a common sterilization method, is often used to control the microorganisms in the material. However, it has not been reported which type of radiation source and what doses can sterilize more effectively without affecting the properties of collagen-based corneal repair materials (CCRMs) and have a positive impact on macrophage polarization. In this study, three different radiation sources of ultraviolet, cobalt-60, and electron beam at four different doses of 2, 5, 8, and 10 kGy were used to irradiate CCRMs. The swelling, stretching, transmittance, and degradation of the irradiated CCRMs were characterized, and the proliferation of human corneal epithelial cells on the irradiated CCRMs was characterized using the CCK8 kit. The results showed that low dose (<5 kGy) of radiation had little effect on the performance of CCRMs. Three irradiation methods with less influence were selected for the further study on RAW264.7 macrophage polarization. The results indicated that CCRMs treated with UV could downregulate the expression of pro-inflammatory related genes and upregulate the expression of anti-inflammatory genes in macrophages, which indicated that UV irradiation is a beneficial process for the preparation of CCRMs.

Contribution of Necroptosis to Myofiber Death in Idiopathic Inflammatory Myopathies.

OBJECTIVE: Myofiber necrosis is a significant pathologic characteristic of idiopathic inflammatory myopathies (IIMs), and its molecular mechanism is largely unknown. Necroptosis is a recently identified form of regulated necrotic cell death, and its activation might have crucial biologic consequences. The aim of the present study was to investigate the role of necroptosis in IIM muscle damage. METHODS: Western blot and immunohistochemistry analyses were performed to examine the expression of receptor-interacting protein 3 (RIP-3) and mixed-lineage kinase domain-like (MLKL) proteins in 26 IIM patients and 4 healthy controls, as well as necroptosis-related damage-associated molecular pattern molecules. Tumor necrosis factor (TNF) was used to stimulate cultured C2C12 myoblasts, and the involvement of necroptosis in cell death of C2C12 cells was studied in vitro. RESULTS: The expression of RIP-3 and MLKL proteins and their phosphorylated forms was significantly increased in the muscle tissue of IIM patients compared to that of healthy controls. The expression levels of RIP-3 and MLKL proteins were associated with the severity of muscle damage in patients with IIM. Significant colocalization of MLKL with high mobility group box chromosomal protein 1 in necrotizing myofibers was observed in muscle biopsy tissue from patients with IIM. Stimulation of C2C12 myoblasts with TNF and a pan-caspase inhibitor, Z-VAD, resulted in the overactivation of necroptosis and significantly increased necrotic cell death. Strategies involving either inhibition of necroptosis with necrostatin-1 or knockdown of MLKL expression successfully prevented necroptosis-induced cell death of C2C12 cells. CONCLUSION: These findings demonstrate that overactivated necroptosis contributes to muscle damage in IIMs and suggest that necroptosis inhibitors could represent a new therapeutic target in the treatment of IIMs.