Isolation, characterization, and circulation sphere of a filovirus in fruit bats.

Bats are associated with the circulation of most mammalian filoviruses (FiVs), with pathogenic ones frequently causing deadly hemorrhagic fevers in Africa. Divergent FiVs have been uncovered in Chinese bats, raising concerns about their threat to public health. Here, we describe a long-term surveillance to track bat FiVs at orchards, eventually resulting in the identification and isolation of a FiV, Dehong virus (DEHV), from Rousettus leschenaultii bats. DEHV has a typical filovirus-like morphology with a wide spectrum of cell tropism. Its entry into cells depends on the engagement of Niemann-Pick C1, and its replication is inhibited by remdesivir. DEHV has the largest genome size of filoviruses, with phylogenetic analysis placing it between the genera Dianlovirus and Orthomarburgvirus, suggesting its classification as the prototype of a new genus within the family Filoviridae. The continuous detection of viral RNA in the serological survey, together with the wide host distribution, has revealed that the region covering southern Yunnan, China, and bordering areas is a natural circulation sphere for bat FiVs. These emphasize the need for a better understanding of the pathogenicity and potential risk of FiVs in the region.

[4D-DIA proteomics reveals mechanism of Sanpian Decoction in treating chronic migraine in rats].

To explore the mechanism of the classic formula Sanpian Decoction in treating chronic migraine, this study employed the four-dimensional data-dependent acquisition(4D-DIA) proteomics to analyze the effect of the decoction on chronic migraine in rats and experimentally verified the key differentially expressed proteins. Firstly, SD male rats were randomly divided into groups and repeatedly injected with nitroglycerin to prepare a chronic migraine model. After 7 consecutive days of gavage, rat grimace scale(RGS) was employed to evaluate the treatment efficacy. The trigeminal ganglion was collected for 4D-DIA proteomics, on the basis of which the diffe-rentially expressed proteins between groups were screened. Multiple databases were used for the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the differentially expressed proteins. STRING and Cytoscape were employed to establish the protein-protein interaction(PPI) network. Western blot was employed to determine the expression level of the key diffe-rentially expressed protein TRPV1. The results showed that there were 517 differentially expressed proteins between blank group and model group and 221 differentially expressed proteins between model group and medium-dose Sanpian Decoction group. The GO and KEGG enrichment results showed that these differentially expressed proteins were mainly related to inflammatory response, injurious sensory stimulation, triglyceride metabolism, immune regulation, etc., which mainly involved the inflammation-related TRP, AMPK, PI3K-Akt, and TGF-ß signaling pathways. The PPI network showed that the target proteins such as IGF, TOP2A, APOA1, CDK1, TTN, RYR1, and CSRP3 had high degrees. Compared with that in model group, the expression level of TRPV1 altered in medium-and high-dose Sanpian Decoction group(P<0.05). In conclusion, Sanpian Decoction may treat chronic migraine by regulating the inflammation-related pathways such as TRP, AMPK, and PI3K-Akt. It plays an important role in the regulation of TRPV1 protein and potentially modulates the perception of injurious stimuli, lipid metabolism, and immune responses.

Comprehensive analysis of m6A regulators characterized by the immune microenvironment in Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked, incurable, degenerative neuromuscular disease that is exacerbated by secondary inflammation. N6-methyladenosine (m6A), the most common base modification of RNA, has pleiotropic immunomodulatory effects in many diseases. However, the role of m6A modification in the immune microenvironment of DMD remains elusive. METHODS: Our study retrospectively analyzed the expression data of 56 muscle tissues from DMD patients and 26 from non-muscular dystrophy individuals. Based on single sample gene set enrichment analysis, immune cells infiltration was identified and the result was validated by flow cytometry analysis and immunohistochemical staining. Then, we described the features of genetic variation in 26 m6A regulators and explored their relationship with the immune mircoenvironment of DMD patients through a series of bioinformatical analysis. At last, we determined subtypes of DMD patients by unsupervised clustering analysis and characterized the molecular and immune characteristics in different subgroups. RESULTS: DMD patients have a sophisticated immune microenvironment that is significantly different from non-DMD controls. Numerous m6A regulators were aberrantly expressed in the muscle tissues of DMD and inversely related to most muscle-infiltrating immune cell types and immune response-related signaling pathways. A diagnostic model involving seven m6A regulators was established using LASSO. Furthermore, we determined three m6A modification patterns (cluster A/B/C) with distinct immune microenvironmental characteristics. CONCLUSION: In summary, our study demonstrated that m6A regulators are intimately linked to the immune microenvironment of muscle tissues in DMD. These findings may facilitate a better understanding of the immunomodulatory mechanisms in DMD and provide novel strategies for the treatment.

[Eleven new sesquiterpenoids from peeled stems of Syringa pinnatifolia].

The peeled stems of Syringa pinnatifolia(SP) is a representative Mongolian folk medicine with the effects of anti-depression, heat clearance, pain relief, and respiration improvement. It has been clinically used for the treatment of coronary heart disease, insomnia, asthma, and other cardiopulmonary diseases. As part of the systematic study on pharmacological substances of SP, 11 new sesquiterpenoids were isolated from the terpene-containing fractions of the ethanol extract of SP by liquid chromatography-mass spectrometry(LC-MS) and proton nuclear magnetic resonance(~1H-NMR) guided isolation methods. The planar structures of the sesquiterpenoids were identified by MS, 1D NMR, and 2D NMR data analysis, and were named pinnatanoids C and D(1 and 2), and alashanoids T-ZI(3-11), respectively. The structure types of the sesquiterpenoids included pinnatane, humulane, seco-humulane, guaiane, carryophyllane, seco-erimolphane, isodaucane, and other types. However, limited to the low content of compounds, the existence of multiple chiral centers, the flexibility of the structure, or lack of ultraviolet absorption, the stereoscopic configuration remained unresolved. The discovery of various sesquiterpenoids enriches the understanding of the chemical composition of the genus and species and provides references for further analysis of pharmacological substances of SP.

Isobaric Stable Isotope N-Phosphorylation Labeling (iSIPL) for Ultrasensitive Proteome Quantification.

Stable isotope chemical labeling methods have been widely used for high-throughput mass spectrometry (MS)-based quantitative proteomics in biological and clinical applications. However, the existing methods are far from meeting the requirements for high sensitivity detection. In the present study, a novel isobaric stable isotope N-phosphorylation labeling (iSIPL) strategy was developed for quantitative proteome analysis. The tryptic peptides were selectively labeled with iSIPL tag to generate the novel reporter ions containing phosphoramidate P-N bond with high intensities under lower collision energies. iSIPL strategy are suitable for peptide sequencing and quantitative analysis with high sensitivity and accuracy even for samples of limited quantity. Furthermore, iSIPL coupled with affinity purification and mass spectrometry was applied to measure the dynamics of cyclin dependent kinase 9 (CDK9) interactomes during transactivation of the HIV-1 provirus. The interaction of CDK9 with PARP13 was found to significantly decrease during Tat-induced activation of HIV-1 gene transcription, suggesting the effectiveness of iSIPL strategy in dynamic analysis of protein-protein interaction in vivo. More than that, the proposed iSIPL strategy would facilitate large-scale accurate quantitative proteomics by increasing multiplexing capability.

Exosomes with FOXP3 from gene-modified dendritic cells ameliorate the development of EAE by regulating the balance of Th/Treg.

Objective: To investigate the efficiency and potential mechanisms of exosomes from dendritic cells (DCs) transfected with Forkhead box protein P3 (FOXP3) in the development of experimental autoimmune encephalomyelitis (EAE). Method: Mouse bone marrow-derived immature DCs were loaded with adenovirus carrying FOXP3 gene, and exosomes were generated. Then the exosomes with FOXP3 (FOXP3-EXOs) were co-cultured with CD4+T cell in vitro to evaluate their potential on CD4+T cell proliferation and differentiation, and injected into EAE mice to assess their effects on the development of EAE. Result: FOXP3-EXOs were effective to inhibit the CD4+T cell proliferation and the production of Interferon gamma (IFN-γ), interleukin (IL)-6, and IL-17, while they promoted the production of IL-10 in vitro. Moreover, FOXP3-EXOs treatment significantly decreased the neurological scores, reduced the infiltration of inflammatory cells into the spinal cord, and decreased demyelination in comparison to saline and Con-EXOs treated EAE mice. Moreover, the FOXP3-EXOs treatment resulted in obvious increases in the levels of regulatory T (Treg) cells and IL-10, whereas levels of T helper 1 (Th1) cells, Th17 cells, IFN-γ, IL-6, and IL-17 decreased significantly in the splenocyte culture of EAE mice. Conclusion: The present study preliminarily investigated the effects and potential mechanisms of FOXP3-EXOs in EAE and revealed that the FOXP3-EXOs could inhibit the production of Th1 and Th17 cells and promote the production of Treg cells as well as ameliorate the development of EAE. The neuroprotective effects of FOXP3-EXOs on EAE are likely due to the regulation of Th/Treg balance.

Phytochemical library screening reveals betulinic acid as a novel Skp2-SCF E3 ligase inhibitor in non-small cell lung cancer.

Skp2 is overexpressed in multiple cancers and plays a critical role in tumor development through ubiquitin/proteasome-dependent degradation of its substrate proteins. Drugs targeting Skp2 have exhibited promising anticancer activity. Here, we identified a plant-derived Skp2 inhibitor, betulinic acid (BA), via high-throughput structure-based virtual screening of a phytochemical library. BA significantly inhibited the proliferation and migration of non-small cell lung cancer (NSCLC) through targeting Skp2-SCF E3 ligase both in vitro and in vivo. Mechanistically, BA binding to Skp2, especially forming H-bonds with residue Lys145, decreases its stability by disrupting Skp1-Skp2 interactions, thereby inhibiting the Skp2-SCF E3 ligase and promoting the accumulation of its substrates; that is, E-cadherin and p27. In both subcutaneous and orthotopic xenografts, BA significantly inhibited the proliferation and metastasis of NSCLC through targeting Skp2-SCF E3 ligase and upregulating p27 and E-cadherin protein levels. Taken together, BA can be considered a valuable therapeutic candidate to inhibit metastasis of NSCLC.

CDKN2A deletions are associated with poor outcomes in 101 adults with T-cell acute lymphoblastic leukemia.

The identification of genetic risk subgroups of T-cell acute lymphoblastic leukemia (T-ALL) may provide evidence for risk stratification and individualized treatment. We investigated the characteristics and prognostic value of tumor suppressor gene CDKN2A deletions in 101 patients with T-ALL. The CDKN2A deletion was present in 23% (23/101) of T-ALL by fluorescence in situ hybridization (FISH). The most common type of CDKN2A deletion was homozygous deletion (70%, 16/23). A lower frequency of CDKN2A deletion was found in patients with early T-cell precursor (ETP) ALL than in patients with non-ETP-ALL (10.4% vs 34.0%; P = .008). Deletion of CDKN2A was significantly associated with younger age (P = .001), higher white blood cell (WBC) count (P < .001) and higher lactate dehydrogenase (LDH) level (P = .002). Patients with CDKN2A deletion had lower 2-year overall survival (OS) and event-free survival (EFS) rates than patients without CDKN2A deletion (2-year OS: 18.6% ± 8.9% vs 47.4% ± 6.2%, P = .032; EFS: 16.4 ± 8.3 vs 38.6 ± 5.9%, P = .022). In multivariable analysis, CDKN2A deletion was an independent adverse prognostic factor for OS (P = .016). In conclusion, adult T-ALL patients with CDKN2A deletion had a poor prognosis, and these patients might benefit from intensive chemotherapy or allogeneic hematopoietic stem-cell transplantation.

GJA1-20k attenuates Ang II-induced pathological cardiac hypertrophy by regulating gap junction formation and mitochondrial function.

Cardiac hypertrophy (CH) is characterized by an increase in cardiomyocyte size, and is the most common cause of cardiac-related sudden death. A decrease in gap junction (GJ) coupling and mitochondrial dysfunction are important features of CH, but the mechanisms of decreased coupling and energy impairment are poorly understood. It has been reported that GJA1-20k has a strong tropism for mitochondria and is required for the trafficking of connexin 43 (Cx43) to cell-cell borders. In this study, we investigated the effects of GJA1-20k on Cx43 GJ coupling and mitochondrial function in the pathogenesis of CH. We performed hematoxylin-eosin (HE) and Masson staining, and observed significant CH in 18-week-old male spontaneously hypertensive rats (SHRs) compared to age-matched normotensive Wistar-Kyoto (WKY) rats. In cardiomyocytes from SHRs, the levels of Cx43 at the intercalated disc (ID) and the expression of GJA1-20k were significantly reduced, whereas JAK-STAT signaling was activated. Furthermore, the SHR rats displayed suppressed mitochondrial GJA1-20k and mitochondrial biogenesis. Administration of valsartan (10 mg· [Formula: see text] d-1, i.g., for 8 weeks) prevented all of these changes. In neonatal rat cardiomyocytes (NRCMs), overexpression of GJA1-20k attenuated Ang II-induced cardiomyocyte hypertrophy and caused elevated levels of GJ coupling at the cell-cell borders. Pretreatment of NRCMs with the Jak2 inhibitor AG490 (10 µM) blocked Ang II-induced reduction in GJA1-20k expression and Cx43 gap junction formation; knockdown of Jak2 in NRCMs significantly lessened Ang II-induced cardiomyocyte hypertrophy and normalized GJA1-20k expression and Cx43 gap junction formation. Overexpression of GJA1-20k improved mitochondrial membrane potential and respiration and lowered ROS production in Ang II-induced cardiomyocyte hypertrophy. These results demonstrate the importance of GJA1-20k in regulating gap junction formation and mitochondrial function in Ang II-induced cardiomyocyte hypertrophy, thus providing a novel therapeutic strategy for patients with cardiomyocyte hypertrophy.

Associations between meteorological variation and rupture of intracranial aneurysm in Fujian, China: A 5-year multicenter study.

OBJECTIVE: By exploring the exposure-response relationships between meteorological factors and rupture of intracranial aneurysm (IA) to reveal the influence of meteorological variation on IA rupture under the specific climate in Fujian, China. METHOD: 7515 cases of IA rupture from several municipal medical institutions in Fujian Province as well as local meteorological data during the same period were collected from 2013 to 2017. Poisson regression and Spearman correlation analysis were applied to explore the distribution characteristics of IA rupture and how it is associated with meteorological parameters. Poisson generalized additive model was established to further analyze the exposure-response relationships between meteorological factors and IA rupture, and its hysteresis effects. RESULT: The IA rupture exhibited a negative correlation with temperature (rs = -0.323, 95% CI: -0.539 ~ -0.068) and a positive correlation with atmospheric pressure (rs = 0.397, 95% CI: 0.152-0.597) or pressure difference (rs = 0.296, 95% CI: 0.038-0.517), 21.05 â„ƒ and 1000.14 hPa were the risk thresholds for the onset ascribed to variation in temperature and atmospheric pressure, respectively. Temperature and atmospheric pressure also exerted hysteresis effects on IA rupture. Cold will increase the rupture risk in the subsequent 1-3 days, and high pressure will raise the morbidity in the next 1-2 days. Besides, drastic variations in temperature and atmospheric pressure were also associated with the higher risk of IA rupture in the next 2 days and 1 day, respectively. CONCLUSION: Temperature and atmospheric pressure have a negative and positive correlation with IA rupture in Fujian, China, respectively. Variation in temperature and atmospheric pressure exert different degrees of hysteresis effects on IA rupture.

Socio-geographical evaluation of ecosystem services in an ecotourism destination: PGIS application in Tram Chim National Park, Vietnam.

Ecotourism in national parks of developing countries is increasingly recognised as a promising option to achieve sustainable development goals, regardless, might imply various paradoxical managerial challenges. This paper, therefore, seeks to contribute a methodological framework utilising ES-based social landscape metrics (SLM) to address the potential barriers in managing ecotourism-integrated multi-functional national parks. We present a mixed-method case study in Vietnam's Tram Chim National Park (TCNP), conducted via semi-structural interviews and PGIS with tourists and locals. Multiple key informants, i.e. TCNP's authorities were also interviewed to provide their managerial insights and assist in verifying the PGIS results obtained from the tourists and locals. Via the quantified and mapped SLMs, the study reveals the differences between tourists and locals in terms of how and where they perceive and appreciate the intangible values of TCNP. Through spatial statistics, we reported important spatial correlations (i) between different categories of Ecosystem Services (ES) and (ii) between ES richness and diversity on different TCNP's land covers. As a contribution to the decision-making outlook, we remarked potential areas to expand of ecotourism activities based on the spatial hot and cold spots. This study concludes by highlighting opportunities for future research in expanding on socio-geographical assessments of ES, especially in the fields of ecotourism.

The deletion of mutant SOD1 via CRISPR/Cas9/sgRNA prolongs survival in an amyotrophic lateral sclerosis mouse model.

The superoxide dismutase 1 (SOD1) mutation is one of the most notable causes of amyotrophic lateral sclerosis (ALS), and modifying the mutant SOD1 gene is the best approach for the treatment of patients with ALS linked to the mutations in this gene. Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas9)/sgRNA delivered by the adeno-associated virus (AAV) system is a powerful tool for genome editing in the central nervous system (CNS). Here, we tested the capacity of the AAV-SaCas9-sgRNA system to modify mutant SOD1 in SOD1G93A transgenic mice and found that AAV9-SaCas9-sgRNA5 deleted the SOD1 gene, improved the lifespan of SOD1G93A mice by 54.6%, and notably ameliorated the performance of ALS transgenic mice. An immunochemical analysis showed that the expression of mutant SOD1 was very weak in motor neurons expressing SaCas9-sgRNA5. Consequently, the area showing muscle atrophy was more notably restored in the group treated with SaCas9-sgRNA5 compared with the group treated with SaCas9-sgLacZ. In addition, deep sequencing did not show the indel mutation in the gene highly matched to sgRNA5. Hence, AAV9-SaCas9-sgRNA-based gene editing is a feasible potential treatment for patients with ALS linked to SOD1 mutations.

Performance of commercially available anti-HDV enzyme-linked immunosorbent assays in Taiwan.

BACKGROUND: Hepatitis D virus (HDV) infection is a major global health issue around the world. There are approximately 15-20 million individuals infected with HDV worldwide. HDV infection usually causes increased mortality compared with infection with hepatitis B virus (HBV) alone. However, testing for the detection of HDV is not widely available in Taiwan. Therefore, the General Biologicals Corporation (GB) HDV Ab kit was developed for detecting anti-HDV antibodies. METHODS: A total of 913 serum and 462 EDTA-treated plasma samples were obtained from HBsAg-positive individuals in three hospitals in Taiwan from June 2014 to November 2017. We used three commercially available ELISA kits, DiaPro HDV Ab, DiaSorin ETI-AB-DELTAK-2 and GB HDV Ab, which were utilized strictly according to the instructions of the manufacturers. RESULTS: A comparative study of the results from the GB HDV Ab kit and the other commercial ELISA kits (DiaPro and DiaSorin) was performed to determine their efficacy for anti-HDV detection. The results indicated that the sensitivity of the GB HDV Ab kit for serum and EDTA samples was 100% compared to that of the DiaPro and DiaSorin kits, whereas the specificity for serum and EDTA samples was 99.3 and 98.1%, respectively. In addition, the overall agreement of the results of the GB HDV Ab kit for the serum and EDTA samples was 99.3 and 98.3%, respectively. It is worth noting that the performance of the GB HDV Ab kit was not affected by interference from triglyceride, bilirubin, hemoglobin, or human anti-mouse antibody. The limit of detection of the GB HDV Ab kit is approximately 100-fold lower than that of the other two commercial kits. CONCLUSIONS: The GB HDV Ab kit, which presented equivalent sensitivity and specificity compared to both certified anti-HDV kits, would be a suitable kit for HDV diagnosis in Taiwan.

Prevalence of infections and antimicrobial use among hemodialysis outpatients: A prospective multicenter study.

Hemodialysis patients are vulnerable to infectious diseases and frequent receipt of antimicrobial agents. The aim of this study was to describe the prevalence and characteristics of infections and antimicrobials use among hemodialysis outpatients. We utilized the dialysis event surveillance protocol developed by the National Healthcare Safety Network to conduct a prospective multicenter study in Anhui, China. A total of 41 dialysis centers involving 7393 outpatients were included. Fistula was the most common type of vascular access (85.3%), followed by tunneled central line (12.7%), and non-tunneled central line (1.2%). There were 118 dialysis events with an overall pooled events rate of 1.60 per 100 patient-months. Intravenous antimicrobial start, positive blood culture, and pus, redness, or increased swelling at the vascular access site were detected at rates of 0.91, 0.23, and 0.46 per 100 patient-months, respectively. The prevalence of dialysis events was commonly higher in patients with a central line, and lower in patients with a fistula. Hemodialysis outpatients also had the noteworthy risks of nonaccess infections. Older age, female gender, and having a central line were associated with the increased risk of dialysis events. Findings recommend that regular monitoring and improvement strategies are warranted in management of infections among hemodialysis outpatients.

6-O-angeloylplenolin exerts neuroprotection against lipopolysaccharide-induced neuroinflammation in vitro and in vivo.

Neuroinflammation is one of the critical events in neurodegenerative diseases, whereas microglia play an important role in the pathogenesis of neuroinflammation. In this study, we investigated the effects of a natural sesquiterpene lactone, 6-O-angeloylplenolin (6-OAP), isolated from the traditional Chinese medicine Centipeda minima (L.) A.Br., on neuroinflammation and the underlying mechanisms. We showed that treatment with lipopolysaccharide (LPS) caused activation of BV2 and primary microglial cells and development of neuroinflammation in vitro, evidenced by increased production of inflammatory cytokines TNF-α and IL-1ß, the phosphorylation and nuclear translocation of NF-κB, and the transcriptional upregulation of COX-2 and iNOS, leading to increased production of proinflammatory factors NO and PGE2. Moreover, LPS treatment induced oxidative stress through increasing the expression levels of NOX2 and NOX4. Pretreatment with 6-OAP (0.5-4 µM) dose-dependently attenuated LPS-induced NF-κB activation and oxidative stress, thus suppressed neuroinflammation in the cells. In a mouse model of LPS-induced neuroinflammation, 6-OAP (5-20 mg·kg-1·d-1, ip, for 7 days before LPS injection) dose-dependently inhibited the production of inflammatory cytokines, the activation of the NF-κB signaling pathway, and the expression of inflammatory enzymes in brain tissues. 6-OAP pretreatment significantly ameliorated the activation of microglia and astrocytes in the brains. 6-OAP at a high dose caused a much stronger antineuroinflammatory effect than dexamethansone (DEX). Furthermore, we demonstrated that 6-OAP pretreatment could inhibit LPS-induced neurite and synaptic loss in vitro and in vivo. In conclusion, our results demonstrate that 6-OAP exerts antineuroinflammatory effects and can be considered a novel drug candidate for the treatment of neuroinflammatory diseases.

Bioinformatics Analysis Identifies Hub Genes and Molecular Pathways Involved in Sepsis-Induced Myopathy.

BACKGROUND Sepsis-induced myopathy (SIM) is a complication of sepsis that results in prolonged mechanical ventilation, long-term functional disability, and increased patient mortality. This study aimed to use bioinformatics analysis to identify hub genes and molecular pathways involved in SIM, to identify potential diagnostic or therapeutic biomarkers. MATERIAL AND METHODS The Gene Expression Omnibus (GEO) database was used to acquire the GSE13205 expression profile. The differentially expressed genes (DEGs) in cases of SIM and healthy controls, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the limma R/Bioconductor software package and clusterProfiler package in R, respectively. The protein-protein interaction (PPI) network data of DEGs was retrieved using the STRING database and analyzed using the Molecular Complex Detection (MCODE) Cytoscape software plugin. RESULTS A total of 196 DEGs were obtained in SIM samples compared with healthy samples, including 93 upregulated genes. The DEGs were significantly upregulated in mineral absorption, and the interleukin-17 (IL-17) signaling pathway and 103 down-regulated genes were associated with control of the bile secretion signaling pathway. A protein-protein interaction (PPI) network was constructed with 106 nodes and 192 edges. The top two important clusters were selected from the PPI by MCODE analysis. There were 16 hub genes with a high degree of connectivity in the PPI network that were selected, including heme oxygenase 1 (HMOX1), nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 (NQO1), and metallothionein (MT)-1E. CONCLUSIONS Bioinformatics network analysis identified key hub genes and molecular mechanisms in SIM.

[Microscopic histochemical comparison during mountain-agarwood formation].

Mountain-agarwood plays an important role in ethnic medicine in China for its pharmaceutical value. Modern pharmacological researches demonstrated that mountain-agarwood was effective for its anti-myocardial ischemia, antibacterial, anti-inflammatory, antitumor and analgesic effects. Mountain-agarwood derives from the peeled roots, stems or twigs of Syringa pinnatifolia which belongs to Syringa genus. It often depends on the purple substance and fragrance to estimate the formation of mountain-agarwood. However, the mechanism of mountain-agarwood formation has not been reported. To observe the microcosmic change in the process during the formation of mountain-agarwood, this study described the microscopic and histochemical characteristics of mountain-agarwood formation through histochemical staining. Our results showed that a significant difference of the distribution of tyloses existed during mountain-agarwood formation. It was observed that inchoate mountain-agarwood had more starch granules and viable cells than mountain-agarwood formed with high level or low level. The amount of polysaccharide and degree of lignification were increased during the mountain-agarwood formation. The results indicated that the mountain-agarwood, which meets the quality requirements for pharmaceutical use, contained the following characteristics: a large amount of purple tyloses in heartwood; yellow-brown tyloses distributing in heartwood and sapwood which were less in the latter; lignification with high level; a few viable cells; lots of polysaccharide and few starch granules in xylem rays cell. This study is aimed to reveal the change of histochemical characteristics during mountain-agarwood formation, and lay the foundation for exploring the mechanism of mountain-agarwood formation.

[An updated phytochemical and pharmacological progress on Syringa pinnatifolia].

Syringa pinnatifolia is an endemic species of Syringa in Oleaceae family in China, mainly distributed in Helan Mountain, which is located between Inner Mongolia and Ningxia. Its peeled roots, stems and thick twigs have been used as Mongolian folk medicine, called "Shan-chen-xiang" in Chinese, for the treatment of coronary heart diseases, angina pectoris and other cardiopulmonary diseases. Modern researches showed that S. pinnatifolia mainly contains lignans, sesquiterpenoids, and volatile oils, and displays anti-myocardial ischemia, sedation, analgesia, antibacterial and other effects. In the past five years, many groups have made new progress on the study of chemical constituents and pharmacological activities of S. pinnatifolia. On the basis of the previous review by our group, this paper summarizes the advances which is beneficial to the development, research and clinical application of S. pinnatifolia, particularly Shan-chen-xiang.

[Analysis of bacterial community structure and diversity during mountain-agarwood formation].

As an important substitute for agarwood, mountain-agarwood, belonging to the family Oleaceae, comes from the root, stem and thick branch of Syringa pinnatifolia, which has a wide range of application in Inner Mongolia, China. It has good clinical efficacy in the use of cardiovascular diseases. However, the formation speed of mountain-agarwood is extremely slow, and its cultivated seedlings have low resin content. Therefore, how to speed up the formation of mountain-agarwood and increase the resin content is a hot research topic in this field. In this work, 16 S rDNA amplicon sequencing method was used to systematically analyze the bacterial communities of different samples of mountain-agarwood. Our data revealed that the samples of mountain-agarwood had more obvious species diversity than the ones of non-mountain-agarwood, especially the wild mountain-agarwood samples. By analysis of bacterial community composition and species abundance, Sphingomonas, Modestobacter and unidentified Cyanobacteria genus were three dominant bacterial genera in all samples. In addition, there are two identified genera of dominant bacteria, namely Actinoplanes and Microbacterium in both wild and cultivated mountain-agarwood, by bacterial community composition and species richness analysis. Meanwhile, Roseomonas was the dominant bacterial genus in both wild and cultivated non-mountain-agarwood samples. Our work could provides basic data for exploring the mechanism of the mountain-agarwood formation, and help to exploit resource of endophytic bacteria reasonably.

Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors.

A series of aryloxyacetic acid derivatives were designed and synthesized as 4-hydoxyphenylpyruvate dioxygenase (HPPD) inhibitors. Preliminary bioassay results reveal that these derivatives are promising Arabidopsis thaliana HPPD (AtHPPD) inhibitors, in particular compounds I12 (K i = 0.011 µM) and I23 (K i = 0.012 µM), which exhibit similar activities to that of mesotrione, a commercial HPPD herbicide (K i = 0.013 µM). Furthermore, the newly synthesized compounds show significant greenhouse herbicidal activities against tested weeds at dosages of 150 g ai/ha. In particular, II4 exhibited high herbicidal activity for pre-emergence treatment that was slightly better than that of mesotrione. In addition, compound II4 was safe for weed control in maize fields at a rate of 150 g ai/ha, and was identified as the most potent candidate for a novel HPPD inhibitor herbicide. The compounds described herein may provide useful guidance for the design of new HPPD inhibiting herbicides and their modification.