A new tetracyclic triterpenoid from endophytic fungus Fusarium sporotrichioides.

Objective: To isolate bioactive compounds from the endophytic fungus Fusarium sporotrichioides isolated from Rauwolfia yunnanensis, and investigate their pharmacological activities. Methods: The chemical constituents were isolated and purified by combining with ODS column chromatography, silica gel column chromatography and by performing semipreparative HPLC. Their structures were established on the basis of 1D NMR (1H-NMR and 13C-NMR) and 2D NMR (1H-1H COSY, HSQC, HMBC and NOESY), as well as HRESIMS and comparison with literature data. In addition, the absolute configuration of compound 1 was determined by calculated ECD data. Results: One previously undescribed tetracyclic triterpenoid derivative, named as integracide L (1), 12α-acetoxy-4,4-dimethyl-24-methylene-5α-cholesta-8,14-diene-2α,3ß,11ß-triol (2), 12α-acetoxy-4,4-dimethyl-24-methylene-5α-cholesta-8-momoene-2α,3ß,11ß-triol (3), 12α-acetoxy-4,4-dimethyl-24-methylene-5α-cholesta-8,14-diene-3ß,11ß-triol (4), and 12α-acetoxy-4,4-dimethyl-24-methylene-5α-cholesta-8-momoene-3ß,11ß-triol (5) were isolated from F. sporotrichioide. Moreover, compound 1 was rare tetracyclic triterpenoid with single methyl replacement at C-4 position. Conclusion: Compound 1 was a new tetracyclic triterpenoid isolated from the endophytic fungus F. sporotrichioides. In addition, compound 2 could inhibit the growth of three different human cancer cells significantly. Compounds 3 and 5 were found to possess better cytotoxic activities on HepG-2 cells than the other compounds, with IC50 values of (2.8 ± 0.1) and (6.3 ± 0.3) µmol/L respectively.

Facile and green synthesis of chlorophyll-derived multi-color fluorescent carbonized polymer dots and their use for sensitive detection of hemin.

Due to the very important role in physiological process, a simple and sensitive hemin detection method is necessarily required. Biomass-based carbonized polymer dots (CPDs) have been widely studied especially as fluorescence probe owing to the advantages of low toxicity and the variety of fluorescence color, yet there are still challenges in developing their multi-color emission property from the same raw materials. In this work, red, white and blue emissive CPDs derived from chlorophyll have been synthesized via hydrothermal method. Then white-emitted CPDs (white-CPDs) with the Commission International d'Eclairage (CIE) coordinates at (0.34, 0.32) were used to develop a fluorescence quenched sensing system for hemin determination. There is a good linear relationship between (F0-F)/F0 and concentration of hemin in the range of 0.1-0.95 µM with a detection limit of 0.043 µM, and the quenching mechanism was considered to be caused by inner filter effect (IFE). Moreover, it has been successfully used for hemin detection in serum and also for visual determination, which indicating great potential in applications of disease diagnoses and trace identification.

Phospholipase A2-activating protein induces mitophagy through anti-apoptotic MCL1-mediated NLRX1 oligomerization.

Mitochondrial protein homeostasis is fine-tuned by diverse physiological processes such as mitochondria-associated degradation (MAD), which is regulated by valosin-containing protein (VCP) and its cofactors. As a cofactor of VCP, the mutation of phospholipase A-2-activating protein (PLAA) is the genetic cause of PLAA-associated neurodevelopmental disorder (PLAAND). However, the physiological and pathological roles of PLAA in mitochondria remain unclear. Here, we demonstrate that PLAA partially associates with mitochondria. Deficiency in PLAA increases mitochondrial reactive oxygen species (ROS) production, reduces mitochondrial membrane potential, inhibits mitochondrial respiratory activity and causes excessive mitophagy. Mechanically, PLAA interacts with myeloid cell leukemia-1 (MCL1) and facilitates its retro-translocation and proteasome-dependent degradation. The upregulation of MCL1 promotes the oligomerization of NLR family member X1 (NLRX1) and activation of mitophagy. Whereas downregulating NLRX1 abolishes MCL1 induced mitophagy. In summary, our data identify PLAA as a novel mediator of mitophagy by regulating MCL1-NLRX1 axis. We propose mitophagy as a target for therapeutic intervention in PLAAND.

Cytotoxic Cyclodepsipeptides and Cyclopentane Derivatives from a Plant-Associated Fungus Fusarium sp.

In this work, four new cyclodepsipeptides, fusarihexins C-E (1-3) and enniatin Q (4), four new cyclopentane derivatives, fusarilins A-D (5-8), together with eight known compounds (9-16), were isolated from cultures of the endophytic fungus Fusarium sp. The structures of the isolated compounds were elucidated by analysis of HRMS and NMR spectroscopic data. The absolute configurations were determined using Marfey's method, a modified Mosher's method, single-crystal X-ray diffraction analysis, and ECD analysis. The antitumor activities of the isolated compounds in vitro were evaluated. Cyclodepsipeptides displayed cytotoxicities against the Huh-7, MRMT-1, and HepG-2 cell lines. Compounds 4, 9, 10, and 12 with IC50 values of 1.0-9.1 µM exhibited the most potent cytotoxicities against the three cell lines as compared to the positive control-5-fluorouracil. Compounds 1-3 and 11 exhibited moderate cytotoxic activities (IC50 values of 10.7-20.1 µM).

Plasma-Assisted Fabrication of Molecularly Imprinted NiAl-LDH Layer on Ni Nanorod Arrays for Glyphosate Detection.

An inorganic-framework molecularly imprinted NiAl layered double hydroxide (MI-NiAl-LDH) with specific template molecule (glyphosate pesticide, Glyp) recognition ability was prepared on Ni nanorod arrays (Ni NRAs) through electrodeposition followed by a low-temperature O2 plasma treatment. The freestanding Ni/MI-NiAl-LDH NRA electrode had highly enhanced sensitivity and selectivity. The electrocatalytic oxidation of Glyp was proposed to occur at Ni3+ centers in MI-NiAl-LDH, and the current response depended linearly on the Glyp concentration from 10.0 nmol/L to 1.0 µmol/L (R2 = 0.9906), with the limit of detection (LOD) being 3.1 nmol/L (S/N = 3). An exceptional discriminating capability with tolerance for other similar organophosphorus compounds was achieved. Molecular imprinting (N and P residues) affected the electronic structure of NiAl-LDH, triggering the formation of highly active NiOOH sites at relatively lower anodic potentials and substantially enhancing the electrocatalytic oxidation ability of the NiAl-LDH interface toward the C-N bonds in Glyp. In combination with the surface enrichment effect of MI-NiAl-LDH toward template molecules, the electrochemical oxidation signal intensity of Glyp increased significantly, with a greater peak separation from interfering molecules. These results challenge the common belief that the excellent performance of inorganic-framework molecularly imprinted interfaces arises from their specific adsorption of template molecules, providing new insight into the development of high-performance organic-pollutant-sensing electrodes.

Mitochondrial HSF1 triggers mitochondrial dysfunction and neurodegeneration in Huntington's disease.

Aberrant localization of proteins to mitochondria disturbs mitochondrial function and contributes to the pathogenesis of Huntington's disease (HD). However, the crucial factors and the molecular mechanisms remain elusive. Here, we found that heat shock transcription factor 1 (HSF1) accumulates in the mitochondria of HD cell models, a YAC128 mouse model, and human striatal organoids derived from HD induced pluripotent stem cells (iPSCs). Overexpression of mitochondria-targeting HSF1 (mtHSF1) in the striatum causes neurodegeneration and HD-like behavior in mice. Mechanistically, mtHSF1 facilitates mitochondrial fission by activating dynamin-related protein 1 (Drp1) phosphorylation at S616. Moreover, mtHSF1 suppresses single-stranded DNA-binding protein 1 (SSBP1) oligomer formation, which results in mitochondrial DNA (mtDNA) deletion. The suppression of HSF1 mitochondrial localization by DH1, a unique peptide inhibitor, abolishes HSF1-induced mitochondrial abnormalities and ameliorates deficits in an HD animal model and human striatal organoids. Altogether, our findings describe an unsuspected role of HSF1 in contributing to mitochondrial dysfunction, which may provide a promising therapeutic target for HD.

DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with Down syndrome.

Down syndrome (DS), caused by trisomy of chromosome 21, occurs in 1 of every 800 live births. Early defects in cortical development likely account for the cognitive impairments in DS, although the underlying molecular mechanism remains elusive. Here, we performed histological assays and unbiased single-cell RNA-Seq (scRNA-Seq) analysis on cerebral organoids derived from 4 euploid cell lines and from induced pluripotent stem cells (iPSCs) from 3 individuals with trisomy 21 to explore cell-type-specific abnormalities associated with DS during early brain development. We found that neurogenesis was significantly affected, given the diminished proliferation and decreased expression of layer II and IV markers in cortical neurons in the subcortical regions; this may have been responsible for the reduced size of the organoids. Furthermore, suppression of the DSCAM/PAK1 pathway, which showed enhanced activity in DS, using CRISPR/Cas9, CRISPR interference (CRISPRi), or small-molecule inhibitor treatment reversed abnormal neurogenesis, thereby increasing the size of organoids derived from DS iPSCs. Our study demonstrates that 3D cortical organoids developed in vitro are a valuable model of DS and provide a direct link between dysregulation of the DSCAM/PAK1 pathway and developmental brain defects in DS.

Xanthones and anthraquinones from the soil fungus Penicillium sp. DWS10-P-6.

Two new xanthones, oxisterigmatocystins J and K (1-2), and two new anthraquinones, versicolorins D and E (3-4), were isolated from solid cultures of the fungus Penicillium sp. DWS10-P-6, together with twelve known compounds (5-16). Their structures, including their absolute configurations, were characterized on the basis of extensive 1D NMR, 2D NMR, MS and CD spectral data. The cytotoxic activities of compounds 1-12 against HL-60, MDA-MB-231 and PC-3 cells were also evaluated. Compounds 4 and 5 showed significant cytotoxic activity against the HL-60 cell line with IC50 values of 1.65 µM and 1.05 µM, respectively.

Prognostic significance of combined pretreatment body mass index (BMI) and BMI loss in patients with esophageal cancer.

Background: Body mass index (BMI) has been associated with a risk of esophageal cancer. However, the influence of BMI and BMI loss on people with esophageal cancer that were treated with different therapies has not been described in China. Methods: In total, 615 consecutive patients that underwent esophagectomy and/or chemotherapy/radiotherapy were classified according to the Asian-specific BMI (kg/m2) cutoff values. The impact of BMI and BMI loss on long-term overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazard models. Results: Multivariate analysis showed that overweight and obese patients had a more favorable survival than normal weight and underweight patients (p=0.017). Patients with a low BMI and high BMI loss before therapy had worse OS than others (p=0.001). Subgroup analysis showed that patients with a high BMI were more likely to suffer hypertension (p<0.001) and receive only surgery (p<0.001), and they were less likely to be smokers (p=0.007) and anemic (p<0.001). Conversely, patients with high BMI loss were more likely to be anemic (p=0.001), to have advanced pathological stage (p=0.012), and to receive chemotherapy and radiotherapy (p=0.001). Moreover, the mortality rate was higher when patients had a high BMI loss. There is no survival benefit of higher BMI in the non-esophageal squamous cell carcinoma (ESCC) group. Conclusion: Pretreatment BMI was an independent prognostic factor for long-term survival in esophageal cancer patients treated with different treatments. The overall survival was increased in esophageal cancer patients with a high pretreatment BMI and no BMI loss. There is no survival benefit of higher BMI in the non-ESCC group.

A facile liquid/liquid interface method to synthesize graphyne analogs.

An innovative facile interfacial synthetic strategy is demonstrated as a general method for the synthesis of graphyne analogs (GYs), which are composed of benzene rings connected by acetylenic bonds. All these synthesized GYs, which are obtained as uniform films in microscopic morphology, exhibit outstanding conductive properties, endowing excellent applications in many electrical devices.

Mutant huntingtin inhibits the mitochondrial unfolded protein response by impairing ABCB10 mRNA stability.

Numerous studies have shown that mitochondrial dysfunction contributes to consequential phenotypes of Huntington's disease (HD), a fatal and inherited neurodegenerative disease caused by the expanded CAG repeats in the N-terminus of the huntingtin (Htt) gene. To maintain proper function, mitochondria develop a dedicated protein quality control mechanism by activating a stress response termed the mitochondrial unfolded protein response (UPRmt). Defects in the UPRmt have been linked to aging and are also associated with neurodegenerative diseases. However, little is known about the role of the UPRmt in HD. In this study, we find that ABCB10, a mitochondrial transporter involved in the UPRmt pathway, is downregulated in HD mouse striatal cells, HD patient fibroblasts, and HD R6/2 mice. Deletion of ABCB10 causes increased mitochondrial reactive oxygen species (ROS) production and cell death, whereas overexpression of ABCB10 reduces these aberrant events. Moreover, the mitochondrial chaperone HSP60 and mitochondrial protease Clpp, two well-established markers of the UPRmt, are reduced in the in vitro ABCB10-deficienct HD models. CHOP, a key transcription factor of HSP60 and Clpp, is regulated by ABCB10 in HD mouse striatal cells. Furthermore, we find that mutant huntingtin (mtHtt) inhibits the mtUPR by impairing ABCB10 mRNA stability. These findings demonstrate a suppression of the UPRmt by mtHtt, suggesting that disturbance of mitochondrial protein quality control may contribute to the pathogenesis of HD.

Optimal river monitoring network using optimal partition analysis: a case study of Hun River, Northeast China.

River monitoring networks play an important role in water environmental management and assessment, and it is critical to develop an appropriate method to optimize the monitoring network. In this study, an effective method was proposed based on the attainment rate of National Grade III water quality, optimal partition analysis and Euclidean distance, and Hun River was taken as a method validation case. There were 7 sampling sites in the monitoring network of the Hun River, and 17 monitoring items were analyzed once a month during January 2009 to December 2010. The results showed that the main monitoring items in the surface water of Hun River were ammonia nitrogen (NH4+-N), chemical oxygen demand, and biochemical oxygen demand. After optimization, the required number of monitoring sites was reduced from seven to three, and 57% of the cost was saved. In addition, there were no significant differences between non-optimized and optimized monitoring networks, and the optimized monitoring networks could correctly represent the original monitoring network. The duplicate setting degree of monitoring sites decreased after optimization, and the rationality of the monitoring network was improved. Therefore, the optimal method was identified as feasible, efficient, and economic.

Regulatory T cells and CD20+ B cells in pediatric very severe aplastic anemia: possible clinical markers for evaluating the therapeutic efficacy and prognosis.

OBJECTIVES: To investigate the immune status of children with very severe aplastic anemia (VSAA), and evaluate the frequencies of CD20+ B cells and Regulatory T cells (Tregs) as potential markers for evaluating the therapeutic efficacy and prognosis. METHODS: We systematically analyzed CD20+ B cells and Tregs using Flow Cytometry in 36 children with VSAA (14 newly diagnosed cases and 22 cases in remission after therapy with HDIVIG + r-ATG + CSA). RESULTS: In newly diagnosed VSAA patients, the percentage of CD20+ B cells was higher than that in healthy children (P < .01), whereas the percentage of Tregs was lower than that in healthy children (P < .001). After treatment with HDIVIG + r-ATG + CSA, the percentage of CD20+ B cells in peripheral blood was decreased obviously, and the percentage of Tregs was significantly increased. CONCLUSION: There is a moderate negative correlation between the percentage of Tregs and CD20+ B cells in our study. Our results shed light on the roles of Tregs and CD20+ B cells as therapeutic efficacy and prognostic markers of pediatric VSAA. Moreover, the mechanism underlying the decrease of blood Tregs and increase of CD20+ B cells in pediatric VSAA patients have been discussed, indicating that Tregs may suppress B cell responses.

Salinicola tamaricis sp. nov., a heavy-metal-tolerant, endophytic bacterium isolated from the halophyte Tamarix chinensis Lour.

A Gram-stain-negative, rod-shaped bacterium, strain F01T, was isolated from leaves of Tamarix chinensis Lour. The isolate grew optimally at 30 °C, at pH 7.0 and with 5.0 % (w/v) NaCl, and showed a high tolerance to manganese, lead, nickel, ferrous ions and copper ions. The major fatty acids were C18 : 1ω7c and C16 : 0, and the predominant respiratory quinone was Q-9. Polar lipids were dominated by diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, unidentified aminoglycolipids and phospholipids. The DNA G+C content was 65.8 %. Based on multilocus phylogenetic analysis, strain F01T belonged to the genus Salinicola, with highest 16S rRNA gene sequence similarity to Salinicola peritrichatus CGMCC 1.12381T (97.7 %). The level of DNA-DNA hybridization between strain F01T and closely related Salinicola strains was well below 70 %. According to the phenotypic, genetic and chemotaxonomic data, strain F01T is considered to represent a novel species in the genus Salinicola, for which the name Salinicola tamaricis sp. nov. is proposed. The type strain is F01T (=CCTCC AB 2015304T=KCTC 42855T).

[Breeding habitat characteristics of red-crowned crane at Zhalong of Northeast China: a multi-scale approach based on TM and ASAR image data].

Based on the Landsat TM and Envisat ASAR HH/HV imagery data and by using the GPS data of red-crowned crane nesting sites (n = 28) at Zhalong National Nature Reserve of Northeast China, the models of the breeding habitat selection of red-crowned crane at the Reserve were established by binary Logistic regression to identify the key variables for the habitat selection at eight spatial scales (30-240 m). The relative performance of the two models based on the Landsat TM and Envisat ASAR HH/HV databases was compared, and the prediction capacity of the models across the eight scales was approached. The overall precisions of the two models were satisfactory (> or = 69.0%). At scale 30 m, only variable TCA_2 entered with negative value into the model based on Landsat TM database, which indicated that the crane at this scale avoided selecting higher density reed marshes. At scales 60-120 m, the variable PCA_2 entered with positive value into the two models, indicating that the crane at these scales had higher demand of high density reed marshes to improve its concealment. At scale 90 m, the variable HV backward scatting coefficient also entered into the combined model, which indicated that water condition was the important factor for the habitat selection of the crane at this scale. At scales > 120 m, the texture information of the two satellite sensors started to be involved into the two models, indicating that at larger scales, the crane had decreasing demand on the vegetation features for its breeding habitat selection but increasing sensitivity to the anthropogenic disturbance factors. The introduction of ASAR variables into the models increased the prediction accuracy of the models markedly at all scales.

[Spatiotemporal dynamics and landscape pattern of alien species Spartina alterniflora in Yancheng coastal wetlands of Jiangsu Province, China].

Based on the 1992-2007 remote sensing images and field survey data, and by using the landscape ecology theories and the method of conversion matrix, the spatiotemporal dynamics and landscape pattern of Spartina alterniflora in Yancheng coastal wetlands were analyzed by GIS. The results showed that the total area of S. alterniflora along the whole coastal beaches of Yancheng increased from 3561 hm2 in 1992 to 14491 hm2 in 2007, with a growth rate of 306.94%. In 1992-2007, the total area of S. alterniflora conversion-in and conversion-out was 26291 hm2 and 15361 hm2, respectively, and the S. alterniflora community in the core area of Yancheng National Nature Reserve expanded from 597 hm2 to 2814 hm2, with an annual growth rate of 24.74%. The S. alterniflora community transformed from scattered patches in estuarine regions into continuous belt pattern mainly distributed in the periphery of coastal wetlands from Sheyang River to Liangduo River. Its centroid moved to the southeast, with a distance of 2.92 km. The average area of patches increased from 1992 to 2002, and then decreased from 2002 to 2007. The largest patch index and area-weighted contiguity index increased year by year, and the shape of patches tended to be more regular.