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Lateolabrax japonicus , a prevalent aquatic delicacy, is known to elicit allergic reactions in certain individuals. Nevertheless, the investigation into its allergenic components has remained notably inadequate. In the research, an approximately 35 kDa heat-stable protein of L. japonicus raw/steamed extracts was verified as tropomyosin (TM) by LC-MS/MS. Open reading frame of TM (852 bp) was acquired via PCR amplification, encoding 284 amino acids. The IgE-binding frequency of TM expressed in Escherichia coli was 22.5% among 80 fish-sensitized patients. Furthermore, TM had the ability to activate basophils in 7 patients. In the Balb/c mice model, compared with the PBS group, the levels of specific antibodies (IgE, IgG1, and IgG2a), CD19 + B cells, IL-4, and IL-10 were significantly increased in the TM group. However, the opposite was indeed the case for CD4 + TCR-β, CD4 + CD25 + Fox p 3 + cells, and IFN-γ. These findings regarding an allergen assist in conducting component-resolved diagnoses and therapeutic research for fish allergy.

Food allergy incidents resulting from the consumption of Mactra quadrangularis is frequently reported. Investigating the impact of the Maillard reaction on the allergenicity of M. quadrangularis allergens is beneficial for the development of hypoallergenic mollusks aquatic products. This study examined the effects of the reaction products (Mactra-Xyl) on the allergenicity using Maillard reaction between crude extract (Mactra) of M. quadrangularis and xylose. The IgE-binding activity with sera from M. quadrangularis allergic patients and allergenicity potential by a mouse food allergy model of Mactra-Xyl were evaluated. Structural changes of Mactra-Xyl were analyzed by UV spectroscopy and surface hydrophobicity assessment, and the amino acid modification sites of the major allergen tropomyosin were further identified using LC-MS/MS. The sera results showed that the IgE-binding activity of Mactra-Xyl was reduced by 56.66 % ± 15.48 % compared to Mactra. In the BALB/c mouse food allergy model, the levels of specific IgE antibody and CD4 + IL-4 + cells were significantly decreased, whereas the levels of IgG2a antibody and CD4 + IFN-γ + cells were observably increased in Mactra-Xyl group compared to those observed in Mactra group, thereby alleviating the allergic response. Furthermore, the UV fluorescence intensity and protein surface hydrophobicity of Mactra-Xyl were decreased. LC-MS/MS results revealed that 6 amino acid residues (K 21 , R 77 , K 86 , R 140 , K 189 , N 202 ) on 4 IgE epitopes of tropomyosin in Mactra-Xyl were modified, the finding explain the reduced allergenicity of Mactra-Xyl. Therefore, this study provided a theoretical basis for the development of hypoallergenic M. quadrangularis products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The increasing concentrations of heavy metals in livestock wastewater pose a serious threat to the environmental safety and human health, limiting its resource utilisation. In the present study, microalgae and nanoscale zero-valent iron were selected to construct a coupled system for copper-containing wastewater treatment. The addition of 50 mg·L -1 nanoscale zero-valent iron (50 nm) was the optimal value for the experiment, which could significantly increase the biomass of microalgae. In addition, nanoscale zero-valent iron stimulated microalgal secretion of extracellular polymeric substances, increasing the contents of binding sites, organic ligands, and functional groups on the microalgal surfaces and ultimately promoting the settling of microalgae and binding of heavy metals. The coupled system could quickly adapt to copper-containing wastewater of 10 mg·L -1 , and the copper removal rate reached 94.99%. Adsorption and uptake by organisms, together with the contribution of zero-valent iron nanoparticles, are the major copper removal pathways. Overall, this work offers a novel technical solution for enhanced treatment of copper-containing livestock wastewater, which will help improve the efficiency and quality of wastewater treatment.

Background: Sinorhizobium meliloti is noted for its exceptional capacity to produce unsaturated fatty acids (UFAs). Earlier studies have indicated that S. meliloti primarily employs the FabA-FabB pathway for UFA synthesis, however, the mechanisms remain elusive. This study was conducted to elucidate these mechanisms responsible for the significant UFA production in S. meliloti., Methods: The genes encoding enoyl-acyl carrier protein (ACP) reductase (ENR) were disrupted using the suicide plasmid pK18mobsacB, followed by the creation of single-crossover and double-crossover mutants. The ENR proteins were expressed in Escherichia coli BL21(DE3) strains and subsequently purified. Their enzymatic activities were assessed through gel electrophoresis and NADH oxidation assays. Additionally, the fatty acid composition was determined using gas chromatography-mass spectrometry (GC-MS) and thin-layer chromatography., Results: Our findings demonstrate that the heterologous expression of fabI2 in a temperature-sensitive E. coli fabI mutant results in a significant enhancement of UFA production. Genetic analyses confirmed that fabI2 is an indispensable gene in the S. meliloti genome, as it cannot be disrupted. Interestingly, we observed that fabI2 could only be functionally replaced by the Enterococcus faecalis fabI gene and not by the homologous fabI1 from S. meliloti, E. coli fabI, or Pseudomonas aeruginosa fabV. Furthermore, we validated that the deletion of fabI1 in S. meliloti triggered an increase in UFA production compared to the wild-type strain Rm1021., Conclusions: In this study, we identified the ENR, encoded by the S. meliloti SMc00326 gene (fabI2), as playing a pivotal role in the biosynthesis of UFAs. Additionally, the FabI1 enzyme, encoded by SMc00005, was found to modulate the fatty acid composition within S. meliloti. Together, these discoveries establish a foundation for the development of a model that explains the significant contribution of FabI2 to the robust synthesis of UFAs in S. meliloti., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

4'-Phosphopantetheinyl transferases (PPTases) play important roles in the posttranslational modifications of bacterial carrier proteins, which are involved in various metabolic pathways. Here, we found that RsacpS and RspcpS encoded a functional AcpS-type and Sfp-type PPTase, respectively, in Ralstonia solanacearum GMI1000, and both are capable of modifying R. solanacearum AcpP1, AcpP2, AcpP3, and AcpP5 proteins. RspcpS is located on the megaplasmid, which does not affect strain growth and fatty acid synthesis but significantly contributes to the virulence of R. solanacearum and preferentially participates in secondary metabolism. We found that deletion of RspcpS did not affect the abilities of cellulose degradation, biofilm formation, and resistance to NaCl, sodium dodecyl sulfate, and H 2 O 2 and attenuated R. solanacearum pathogenicity only in the assay of soil-drenching infection but not stem injection of tomato. It is hypothesized that RsPcpS plays a role in cell viability in complex environments and in the process during which the strain recognizes and approaches plants. These results suggest that both RsAcpS and RsPcpS may be potential targets for controlling diseases caused by R. solanacearum ., Competing Interests: The author(s) declare no conflict of interest.

Background: The beet webworm, Loxostege sticticalis, a worldwide pest of many crops, performs a seasonal migration, causing periodic outbreaks in Asia, Europe and North America. Although long-distance migration is well documented in China, patterns of transboundary migration among China, Russia and Mongolia are largely unknown. We performed a phase analysis of L. sticticalis periodic outbreaks among three countries based on 30 years of historical population data, analyzed the wind systems during migration over boundary regions, and traced the migratory routes in a case study of outbreaks in 2008 by trajectory simulation., Results: Highly synchronized outbreak years of L. sticticalis were observed between China and Mongolia, China and eastern Siberia, China and western Siberia, Mongolia and eastern Siberia, eastern Siberia and western Siberia from 1978 to 2008, indicating possible transboundary migration between these regions. Winds at 300-600 m altitude, where adult migration usually occurs, also showed a high probability of northwestern winds in Haila'er (China), Chita (Russia) and Choybalsan (Mongolia), favoring successful adult migration from these areas to northern and northeastern China. Back trajectory analysis further showed that the first-generation adults that caused the severe outbreak of second-generation larvae in 2008 originated from eastern Siberia, eastern Mongolia, and the boundary regions of China-Russia and China-Mongolia., Conclusion: Our findings demonstrated that the source of L. sticticalis outbreaks in northern China was closely related to the outbreaks in Siberia and Mongolia via long-distance transboundary windborne migration. This information will help guide international monitoring and management strategies against this notorious pest. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Tropomyosin (TM) is the main allergen in shrimp ( Litopenaeus vannamei ). In this study, the effects of allergenicity and structure of TM by glycosylation (GOS-TM), phosphate treatment (SP-TM), and glycosylation combined with phosphate treatment (GOS-SP-TM) were investigated. Compared to GOS-TM and SP-TM, the IgG/IgE binding capacity of GOS-SP-TM was significantly decreased with 63.9 ± 2.0 and 49.7 ± 2.7%, respectively. Meanwhile, the α-helix content reduced, surface hydrophobicity increased, and 10 specific amino acids (K 30 , K 38 , S 39 , K 48 , K 66 , K 74 , K 128 , K 161 , S 210 , and K 251 ) were modified by glycosylation on six IgE linear epitopes of GOS-SP-TM. In the BALB/c mice allergy model, GOS-SP-TM could significantly reduce the levels of specific IgE, IgG1, and CD4 + IL-4 + , while the levels of IgG2a, CD4 + CD25 + Foxp3 + , and CD4 + IFN-γ + were increased, which equilibrated Th1 and Th2 cells, thus alleviating allergic symptoms. These results indicated that glycosylation combined with phosphate treatment can provide a new insight into developing hypoallergenic shrimp food.

Recombination is a pervasive phenomenon in RNA viruses and an important strategy for accelerating the evolution of RNA virus populations. Recombination in the porcine reproductive and respiratory syndrome virus (PRRSV) was first reported in 1999, and many case reports have been published in recent years. In this review, all the existing reports on PRRSV recombination events were collected, and the genotypes, parental strains, and locations of the recombination breakpoints have been summarized and analyzed. The results showed that the recombination pattern constantly changes; whether inter- or intra-lineage recombination, the recombination hotspots vary in different recombination patterns. The virulence of recombinant PRRSVs was higher than that of the parental strains, and the emergence of virulence reversion was caused by recombination after using MLV vaccines. This could be attributed to the enhanced adaptability of recombinant PRRSV for entry and replication, facilitating their rapid propagation. The aim of this paper was to identify common features of recombinant PRRSV strains, reduce the recombination risk, and provide a foundation for future research into the mechanism of PRRSV recombination.

Tuberculous tracheobronchial fistulas are caused by mediastinal or hilar tuberculous lymph nodes ulcerating into the trachea or bronchus. Patients usually require flexible bronchoscopic interventional procedures in addition to systemic anti-tuberculosis chemotherapy in the ulceration phase. In this paper, we reported 2 cases of central airway stenosis caused by tuberculous tracheobronchial fistula, which had poor treatment results after flexible bronchoscopy. According to the patients' condition, the airway lesions were treated by rigid bronchoscopy combined with flexible bronchoscopy, cryotherapy, argon plasma coagulation, and so on. The central airway stenosis was resolved quickly, and the caseating lymph node tissue was removed as much as possible under the premise of ensuring safety, which shortened the recovery time of tuberculous fistula.

Three-spot seahorse ( Hippocampus trimaculatus ) has been consumed as traditional Chinese medicine in Asian society. This study was designed to analyze the bioactive compounds of the solvent extracts from cultured three-spot seahorse by high pressure liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI/MS/MS). Subsequently, their biological activities were evaluated and confirmed by cell modes and Western blot analysis. Experimental results indicated that taurine and arginine were the primary bioactive compounds identified and quantified without pre- or post-column derivatization within 20 min retention time. The analytical method was established and validated with intraday/interday RSD from 0.25% to 3.34% and with recovery from 87.8% to 91.2%. As compared to other extracts, water layer extract (WLE) contained the most taurine and arginine contents of 6.807 and 0.437 mg/g (dry basis), respectively. In the meanwhile, WLE also showed anti-inflammatory activity on LPS-induced NO production and inhibited the protein expression of TNF-α and COX-2 by Western blot analysis with better cell viability., Competing Interests: The authors hereby declare that there are no conflicts of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Developing novel cancer therapies that exploit programmed cell death pathways holds promise for advancing cancer treatment. According to a recently published study in Science, copper death (cuproptosis) occurs when intracellular copper is overloaded, triggering aggregation of lipidated mitochondrial proteins and Fe-S cluster proteins. This intriguing phenomenon is triggered by the instability of copper ions. Understanding the molecular mechanisms behind cuproptosis and its associated genes, as identified by Tsvetkov, including ferredoxin 1, lipoic acid synthase, lipoyltransferase 1, dihydrolipid amide dehydrogenase, dihydrolipoamide transacetylase, pyruvate dehydrogenase α1, pyruvate dehydrogenase β, metallothionein, glutaminase, and cyclin-dependent kinase inhibitor 2A, may open new avenues for cancer therapy. Here, we provide a new understanding of the role of copper death and related genes in cancer., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Hepatocellular carcinoma (HCC) is one of the most prevalent tumors worldwide and the leading contributor to cancer-related deaths. The progression and metastasis of HCC are closely associated with altered mitochondrial metabolism, including mitochondrial stress response. Mitokines, soluble proteins produced and secreted in response to mitochondrial stress, play an essential immunomodulatory role. Immunotherapy has emerged as a crucial treatment option for HCC. However, a positive response to therapy is typically dependent on the interaction of tumor cells with immune regulation within the tumor microenvironment. Therefore, exploring the specific immunomodulatory mechanisms of mitokines in HCC is essential for improving the efficacy of immunotherapy. This study provides a comprehensive overview of the association between HCC and the immune microenvironment and highlights recent progress in understanding the involvement of mitochondrial function in preserving liver function. In addition, a systematic review of mitokines-mediated immunomodulation in HCC is presented. Finally, the potential diagnostic and therapeutic roles of mitokines in HCC are prospected and summarized. Recent progress in mitokine research represents a new prospect for mitochondrial therapy. Considering the potential of mitokines to regulate immune function, investigating them as a relevant molecular target holds great promise for the diagnosis and treatment of HCC., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The lumen-occlusion type of tracheobronchial tuberculosis is the most severe type of tracheobronchial stenosis of tuberculosis, often leading to atelectasis or even lung damage in patients. Some patients require surgical resection of the diseased airways and lungs, which can seriously affect their quality of life and even be life-threatening. In order to improve the treatment ability of bronchoscopy physicians for lumen occlusion type of tracheobronchial tuberculosis, this article retrospectively analyzed 30 cases of tracheobronchial tuberculosis with lumen occlusion in Hunan Chest Hospital, and summarized the experience of achieving better results by high-frequency electrotome combined with balloon dilatation and cryotherapy.

Background: While recent studies have separately explored mutational signatures and the tumor microenvironment (TME), there is limited research on the associations of both factors in a pan-cancer context., Materials and Methods: We performed a pan-cancer analysis of over 8,000 tumor samples from The Cancer Genome Atlas (TCGA) project. Machine learning methods were employed to systematically explore the relationship between mutational signatures and TME and develop a risk score based on TME-associated mutational signatures to predict patient survival outcomes. We also constructed an interaction model to explore how mutational signatures and TME interact and influence cancer prognosis., Results: Our analysis revealed a varied association between mutational signatures and TME, with the Clock-like signature showing the most widespread influence. Risk scores based on mutational signatures mainly induced by Clock-like and AID/APOBEC activity exhibited strong pan-cancer survival stratification ability. We also propose a novel approach to predict transcriptome decomposed infiltration levels using genome-derived mutational signatures as an alternative approach for exploring TME cell types when transcriptome data are unavailable. Our comprehensive analysis revealed that certain mutational signatures and their interaction with immune cells significantly impact clinical outcomes in particular cancer types. For instance, T cell infiltration levels only served as a prognostic biomarker in melanoma patients with high ultraviolet radiation exposure, breast cancer patients with high homologous recombination deficiency signature, and lung adenocarcinoma patients with high tobacco-associated mutational signature., Conclusion: Our study comprehensively explains the complex interplay between mutational signatures and immune infiltration in cancer. The results highlight the importance of considering both mutational signatures and immune phenotypes in cancer research and their significant implications for developing personalized cancer treatments and more effective immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Luo, Li, Wei, Ma, Qian, Chen, Wang and Zhao.)

High mobility group A1 (HMGA1) chromatin regulators are upregulated in diverse tumors where they portend adverse outcomes, although how they function in cancer remains unclear. Pancreatic ductal adenocarcinomas (PDACs) are highly lethal tumors characterized by dense desmoplastic stroma composed predominantly of cancer-associated fibroblasts and fibrotic tissue. Here, we uncover an epigenetic program whereby HMGA1 upregulates FGF19 during tumor progression and stroma formation. HMGA1 deficiency disrupts oncogenic properties in vitro while impairing tumor inception and progression in KPC mice and subcutaneous or orthotopic models of PDAC. RNA sequencing revealed HMGA1 transcriptional networks governing proliferation and tumor-stroma interactions, including the FGF19 gene. HMGA1 directly induces FGF19 expression and increases its protein secretion by recruiting active histone marks (H3K4me3, H3K27Ac). Surprisingly, disrupting FGF19 via gene silencing or the FGFR4 inhibitor BLU9931 recapitulates most phenotypes observed with HMGA1 deficiency, decreasing tumor growth and formation of a desmoplastic stroma in mouse models of PDAC. In human PDAC, overexpression of HMGA1 and FGF19 defines a subset of tumors with extremely poor outcomes. Our results reveal what we believe is a new paradigm whereby HMGA1 and FGF19 drive tumor progression and stroma formation, thus illuminating FGF19 as a rational therapeutic target for a molecularly defined PDAC subtype.

Diabetic wounds are challenging to heal due to complex pathogenic abnormalities. Routine treatment with acid fibroblast growth factor (aFGF) is widely used for diabetic wounds but hardly offers a satisfying outcome due to its instability. Despite the emergence of various nanoparticle-based protein delivery approaches, it remains challenging to engineer a versatile delivery system capable of enhancing protein stability without the need for complex preparation. Herein, a polyphenol-driven facile assembly of nanosized coacervates (AE-NPs) composed of aFGF and Epigallocatechin-3-gallate (EGCG) was constructed and applied in the healing of diabetic wounds. First, the binding patterns of EGCG and aFGF were predicted by molecular docking analysis. Then, the characterizations demonstrated that AE-NPs displayed higher stability in hostile conditions than free aFGF by enhancing the binding activity of aFGF to cell surface receptors. Meanwhile, the AE-NPs also had a powerful ability to scavenge reactive oxygen species (ROS) and promote angiogenesis, which significantly accelerated full-thickness excisional wound healing in diabetic mice. Besides, the AE-NPs suppressed the early scar formation by improving collagen remodeling and the mechanism was associated with the TGF-β/Smad signaling pathway. Conclusively, AE-NPs might be a potential and facile strategy for stabilizing protein drugs and achieving the scar-free healing of diabetic wounds. STATEMENT OF SIGNIFICANCE: Diabetic chronic wound is among the serious complications of diabetes that eventually cause the amputation of limbs. Herein, a polyphenol-driven facile assembly of nanosized coacervates (AE-NPs) composed of aFGF and EGCG was constructed. The EGCG not only acted as a carrier but also possessed a therapeutic effect of ROS scavenging. The AE-NPs enhanced the binding activity of aFGF to cell surface receptors on the cell surface, which improved the stability of aFGF in hostile conditions. Moreover, AE-NPs significantly accelerated wound healing and improved collagen remodeling by regulating the TGF-β/Smad signaling pathway. Our results bring new insights into the field of polyphenol-containing nanoparticles, showing their potential as drug delivery systems of macromolecules to treat diabetic wounds., Competing Interests: Declaration of Competing Interest We would like to submit the enclosed manuscript entitled “Polyphenol-driven facile assembly of a nanosized acid fibroblast growth factor-containing coacervate accelerates the healing of diabetic wounds” by Meng-Qi Tong, Cui-Tao Lu, Lan-Tian Huang, Jiao-Jiao Yang, Si-Ting Yang, Hang-Bo Chen, Peng-Peng Xue, Lan-Zi Luo, Qing Yao, He-Lin Xu, Ying-Zheng Zhao, which we wish to be considered for publication in “Acta Biomaterialia”. No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Six new citreoviridins (citreoviridins J-O, 1 - 6 ) and twenty-two known compounds ( 7 - 28 ) were isolated from the deep-sea-derived Penicillium citreonigrum MCCC 3A00169. The structures of the new compounds were determined by spectroscopic methods, including the HRESIMS, NMR, ECD calculations, and dimolybdenum tetraacetate-induced CD (ICD) experiments. Citreoviridins J-O ( 1 - 6 ) are diastereomers of 6,7-epoxycitreoviridin with different chiral centers at C-2-C-7. Pyrenocine A ( 7 ), terrein ( 14 ), and citreoviridin ( 20 ) significantly induced apoptosis for HeLa cells with IC 50 values of 5.4 μ M, 11.3 μ M, and 0.7 μ M, respectively. To be specific, pyrenocine A could induce S phase arrest, while terrein and citreoviridin could obviously induce G0-G1 phase arrest. Citreoviridin could inhibit mTOR activity in HeLa cells.

Myeloproliferative neoplasms (MPNs) transform to myelofibrosis (MF) and highly lethal acute myeloid leukemia (AML), although the actionable mechanisms driving progression remain elusive. Here, we elucidate the role of the high mobility group A1 (HMGA1) chromatin regulator as a novel driver of MPN progression. HMGA1 is upregulated in MPN, with highest levels after transformation to MF or AML. To define HMGA1 function, we disrupted gene expression via CRISPR/Cas9, short hairpin RNA, or genetic deletion in MPN models. HMGA1 depletion in JAK2V617F AML cell lines disrupts proliferation, clonogenicity, and leukemic engraftment. Surprisingly, loss of just a single Hmga1 allele prevents progression to MF in JAK2V617F mice, decreasing erythrocytosis, thrombocytosis, megakaryocyte hyperplasia, and expansion of stem and progenitors, while preventing splenomegaly and fibrosis within the spleen and BM. RNA-sequencing and chromatin immunoprecipitation sequencing revealed HMGA1 transcriptional networks and chromatin occupancy at genes that govern proliferation (E2F, G2M, mitotic spindle) and cell fate, including the GATA2 master regulatory gene. Silencing GATA2 recapitulates most phenotypes observed with HMGA1 depletion, whereas GATA2 re-expression partially rescues leukemogenesis. HMGA1 transactivates GATA2 through sequences near the developmental enhancer (+9.5), increasing chromatin accessibility and recruiting active histone marks. Further, HMGA1 transcriptional networks, including proliferation pathways and GATA2, are activated in human MF and MPN leukemic transformation. Importantly, HMGA1 depletion enhances responses to the JAK2 inhibitor, ruxolitinib, preventing MF and prolonging survival in murine models of JAK2V617F AML. These findings illuminate HMGA1 as a key epigenetic switch involved in MPN transformation and a promising therapeutic target to treat or prevent disease progression., (© 2022 by The American Society of Hematology.)

Fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m 6 A) demethylase, participates in tumor progression and metastasis in many malignancies, but its role in colorectal cancer (CRC) is still unclear. Here, we found that FTO protein levels, but not RNA levels, were downregulated in CRC tissues. Reduced FTO protein expression was correlated with a high recurrence rate and poor prognosis in resectable CRC patients. Moreover, we demonstrated that hypoxia restrained FTO protein expression, mainly due to an increase in ubiquitin-mediated protein degradation. The serine/threonine kinase receptor associated protein (STRAP) might served as the E3 ligase and K216 was the major ubiquitination site responsible for hypoxia-induced FTO degradation. FTO inhibited CRC metastasis both in vitro and in vivo. Mechanistically, FTO exerted a tumor suppressive role by inhibiting metastasis-associated protein 1 (MTA1) expression in an m 6 A-dependent manner. Methylated MTA1 transcripts were recognized by an m 6 A "reader", insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), which then stabilized its mRNA. Together, our findings highlight the critical role of FTO in CRC metastasis and reveal a novel epigenetic mechanism by which the hypoxic tumor microenvironment promotes CRC metastasis., (© 2021. The Author(s).)

Ten new ( 1 - 10 ) and 26 known ( 11 - 36 ) compounds were isolated from Penicillium griseofulvum MCCC 3A00225, a deep sea-derived fungus. The structures of the new compounds were determined by detailed analysis of the NMR and HRESIMS spectroscopic data. The absolute configurations were established by X-ray crystallography, Marfey's method, and the ICD method. All isolates were tested for in vitro anti-food allergic bioactivities in immunoglobulin (Ig) E-mediated rat basophilic leukemia (RBL)-2H3 cells. Compound 13 significantly decreased the degranulation release with an IC 50 value of 60.3 μM, compared to that of 91.6 μM of the positive control, loratadine.

Introduction: The present study aimed to investigate the differences in the proteomic expression between uncomplicated parapneumonic pleural effusion (UPPE) and complicated parapneumonic pleural effusion (CPPE)., Material and Methods: There were 10 patients with UPPE and 10 patients with CPPE. These patients were combined due to the complication of pleural effusion and further divided into group A and group B. An LC-MS analysis was conducted with the extraction of high-abundance proteins, and proteins with 1.5-fold or higher difference multiples were identified as differential proteins. Then, gene ontology (GO) and KEGG analyses were conducted on the differential proteins between the groups., Results: Compared with the UPPE group, there were 38 upregulated proteins and 29 downregulated proteins in the CPPE group. The GO analysis revealed that the CPPE group had enhanced expressions in monosaccharide biosynthesis, glucose catabolism, fructose-6-phosphate glycolysis, glucose-6-phosphate glycolysis, and NADH regeneration as well as reduced expressions in fibrinogen complexes, protein polymerization, and coagulation. Moreover, the KEGG analysis showed that the CPPE group had enhanced expressions in amino acid synthesis, the HIF-1 signalling pathway, and glycolysis/glycoisogenesis and decreased expressions in platelet activation and complement activation., Conclusions: In pleural effusion in patients with CPPE, there are enhanced expressions of proteins concerning glucose and amino acid metabolism, NADH regeneration, and HIF-1 signalling pathways together with decreased expressions of proteins concerning protein polymerization, blood coagulation, platelet activation, and complement activation., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Termedia & Banach.)

Objective: To investigate the efficacy of balloon dilatation performed for patients who suffered from actively caseating endobronchial tuberculosis (EBTB) and central airway stenosis in clinical improving period who's bronchus has not formed mature scar tissue. Methods: A total of 152 tuberculous unilateral main bronchus stenosis patients (23 male and 129 female) who received treatment in Hunan Chest Hospital from January 1 st 2014 to December 31 st 2018 were included in this retrospective analysis. The age was 15-66 (33.3±11.9) years old. All patients received routine anti-tuberculosis chemotherapy. Sixty-four of them who suffered from actively caseating EBTB and unilateral main bronchus stenosis received cryotherapy and endobronchial isoniazid (INH) administration till the caseating necrosis in stenotic bronchus was disappeared and ulcers were recovered, and then received balloon dilatation combined with cryotherapy, were test group. Eighty-eight of them who suffered from fibrostenotic EBTB received balloon dilatation combined with cryotherapy were control group. We analyzed the efficacy and complications after treatments. Results: The lung re-expansion rate after treatment in test group was higher than the control group, and the differences were statistically significant [74.0%(37/50) vs. 37.9%(22/58), χ²= 14.094, P <0.001]. The 6-month re-stenosis rate in test group was lower than control group, and the differences were statistically significant [10.9%(7/64) vs . 30.7% (27/88), χ²= 8.318, P =0.004]. The differences of diameter and diameter variation after balloon dilatation, immediate effective rates, average times of balloon dilatation and procedure-related bleeding (<10 ml) rates, chest pain rates had no statistical signification in two groups. Severe complications including fatal bleeding (>100 ml) and mediastinal emphysema did not occur during our procedures. Conclusions: Performing balloon dilatation for patients who suffered from actively caseating EBTB and central airway stenosis in the clinical improvement period, when caseous necrosis tissue disappeared and ulcers were recovered, not only helps to perform interventional procedures on distal bronchus in time, increase the rate of lung re-expansion, can also reduce the rate of re-stenosis after 6 months, so it is effective and safe.

Diabetic nephropathy (DN) is one of the most serious complications of diabetes mellitus. The combination of insulin (Ins) with liraglutide (Lir) has a greater potential for preventing DN than monotherapy. However, the renal protective effect of the combined Ins/Lir therapy is largely compromised due to their short half-lives after subcutaneous injection. Herein, a glucose-responsive hydrogel was designed in situ forming the dynamic boronic esters bonds between phenylboronic acid-grafted γ-Polyglutamic acid (PBA-PGA) and konjac glucomannan (KGM). It was hypothesized that the KGM/PBA-PGA hydrogel as the delivery vehicle of Ins/Lir would enhance the combinational effect of the latter on preventing the DN progress. Scan electronic microscopy and rheological studies showed that KGM/PBA-PGA hydrogel displayed good glucose-responsive property. Besides, the glucose-sensitive release profile of either Ins or Lir from KGM/PBA-PGA hydrogel was uniformly displayed at hyperglycemic level. Furthermore, the preventive efficacy of KGM/PBA-PGA hydrogel incorporating insulin and liraglutide (Ins/Lir-H) on DN progress was evaluated on streptozotocin-induced rats with diabetic mellitus (DM). At 6 weeks after subcutaneous injection of Ins/Lir-H, not only the morphology of kidneys was obviously recovered as shown by ultrasonography, but also the renal hemodynamics was significantly improved. Meanwhile, the 24-h urinary protein and albumin/creatinine ratio were well modulated. Inflammation and fibrosis were also largely inhibited. Besides, the glomerular NPHS-2 was obviously elevated after treatment with Ins/Lir-H. The therapeutic mechanism of Ins/Lir-H was highly associated with the alleviation of oxidative stress and activation of autophagy. Conclusively, the better preventive effect of the combined Ins/Lir via KGM/PBA-PGA hydrogel on DN progress was demonstrated as compared with their mixed solution, suggesting KGM/PBA-PGA hydrogel might be a potential vehicle of Ins/Lir to combat the progression of DN., Competing Interests: Declaration of Competing Interest We would like to submit the enclosed manuscript entitled “In situ cross-linked glucose-responsive hydrogel by dynamic boronic esters enhances the combinational effect of insulin and liraglutide on preventing the nephropathy progress of diabetic rats” by Ying-Zheng Zhao, Meng-Qi Tong, Lan-Zi Luo, Peng-Peng Xue, Yong-Hui Han, Li-Fen Wang, De-Li Zhuge, Qing Yao, Bin Chen, He-Lin Xu, which we wish to be considered for publication in “Acta Biomaterialia”. No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part., (Copyright © 2021. Published by Elsevier Ltd.)

Superparamagnetic iron oxide nanoparticles (SPIONs) have been presented to regulate the migration and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under magnetic field (MF). However, the toxicity and short residence for the massively exposed SPIONs at bone defects compromises their practical application. Herein, SPIONs were encapsulated into PLGA microspheres to overcome these shortcomings. Three types of PLGA microspheres (PFe-I, PFe-II and PFe-III) were prepared by adjusting the feeding amount of SPIONs, in which the practical SPIONs loading amounts was 1.83%, 1.38% and 1.16%, respectively. The average diameter of the fabricated microspheres ranged from 160 μm to 200 μm, having the porous and rough surfaces displayed by SEM. Moreover, they displayed the magnetic property with a saturation magnetization of 0.16 emu/g. In vitro cell studies showed that most of BMSCs were adhered on the surface of PFe-II microspheres after 2 days of co-culture. Moreover, the osteoblasts differentiation of BMSCs was significantly promoted by PFe-II microspheres after 2 weeks of co-culture, as shown by detecting osteogenesis-related proteins expressions of ALP, COLI, OPN and OCN. Afterward, PFe-II microspheres were surgically implanted into the defect zone of rat femoral bone, followed by exposure to an external MF, to evaluate their bone repairing effect in vivo. At 6th week after treatment with PFe-II + MF, the bone mineral density (BMD, 263.97 ± 25.99 mg/cm 3 ), trabecular thickness (TB.TH, 0.58 ± 0.08 mm), and bone tissue volume/total tissue volume (BV/TV, 78.28 ± 5.01%) at the defect zone were markedly higher than that of the PFe-II microspheres alone (BMD, 194.34 ± 26.71 mg/cm 3 ; TB.TH, 0.41 ± 0.07 mm; BV/TV, 50.49 ± 6.41%). Moreover, the higher expressions of ALP, COLI, OPN and OCN in PFe-II + MF group were displayed in the repairing bone. Collectively, magnetic PLGA microspheres together with MF may be a promising strategy for repairing bone defects., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Bone repair and regeneration processes are markedly impaired in diabetes mellitus (DM). Intervening approaches similar to those developed for normal healing conditions have been adopted to combat DM-associated bone regeneration. However, limited outcomes were achieved for these approaches. Hence, together with osteoconductive hydroxyapatite (HA) nanocrystals, osteoinductive magnesium oxide (MgO) nanocrystals were uniformly mounted into the network matrix of an organic hydrogel composed of cysteine-modified γ-polyglutamic acid (PGA-Cys) to construct a hybrid and rough hydrogel scaffold. It was hypothesized that the HA/MgO nanocrystal hybrid hydrogel (HA/MgO-H) scaffold can significantly promote bone repair in DM rats via the controlled release of Mg 2+ . The HA/MgO-H scaffold exhibited a sponge-like morphology with porous 3D networks inside it and displayed higher mechanical strength than a PGA-Cys scaffold. Meanwhile, the HA/MgO-H scaffold gradually formed a tough hydrogel with G' of more than 1000 Pa after hydration, and its high hydration swelling ratio was still retained. Moreover, after the chemical degradation of the dispersed MgO nanocrystals, slow release of Mg 2+ from the hydrogel matrix was achieved for up to 8 weeks because of the chelation between Mg 2+ and the carboxyl groups of PGA-Cys. In vitro cell studies showed that the HA/MgO-H scaffold could not only effectively promote the migration and proliferation of BMSCs but could also induce osteogenic differentiation. Moreover, in the 8th week after implanting the HA/MgO-H scaffold into femur bone defect zones of DM rats, more effective bone repair was presented by micro-CT imaging. The bone mineral density (397.22 ± 16.36 mg cm -3 ), trabecular thickness (0.48 ± 0.07 mm), and bone tissue volume/total tissue volume (79.37 ± 7.96%) in the HA/MgO-H group were significantly higher than those in the other groups. Moreover, higher expression of COL-I and OCN after treatment with HA/MgO-H was also displayed. The bone repair mechanism of the HA/MgO-H scaffold was highly associated with reduced infiltration of pro-inflammatory macrophages (CD80 + ) and higher angiogenesis (CD31 + ). Collectively, the HA/MgO-H scaffold without the usage of bioactive factors may be a promising biomaterial to accelerate bone defect healing under diabetes mellitus.

Ten new C 9 polyketides (asperochratides A-J, 1-10) and 14 known miscellaneous compounds (11-24) were isolated from the deep-sea-derived fungus Aspergillus ochraceus. Structures of the new compounds were elucidated by extensive spectroscopic analyses, modified Mosher's method, Mo 2 (OAc) 4 induced circular dichroism (ICD) experiments, and ECD calculations. Structurally, compounds 1-11 and 16-18 share the same polyketide origin of the skeleton and belong to aspyrone co-metabolites. All isolates were tested for cytotoxic, anti-food allergic, anti-H1N1 virus, anti-microbe, and anti-inflammatory activities in vitro. Results showed that compounds 5-8 and 13-17 exerted significant cytotoxic effects on BV-2 cell line, and compound 16 showed the potential of anti-inflammatory activities., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To understand the characteristics and differences of diarrhea-related symptoms caused by different pathogens, and the clinical features of various pathogens causing diarrhea. Methods: Etiology surveillance program was conducted among 20 provinces of China from 2010 to 2016. The acute diarrhea outpatients were collected from clinics or hospitals. A questionnaire was used to survey demographics and clinical features. VFeces samples were taken for laboratory detection of 22 common diarrhea pathogens, to detect and analyze the clinical symptom pattern characteristics of the patient's. Results: A total of 38 950 outpatients were enrolled from 20 provinces of China. The positive rates of Rotavirus and Norovirus were the highest among the five diarrhea-causing viruses (Rotavirus: 18.29%, Norovirus: 13.06%). In the isolation and culture of 17 diarrhea-causing bacterial, Escherichia coli showed the highest positive rates (6.25%). The clinical features of bacterial diarrhea and viral diarrhea were mainly reflected in the results of fecal traits and routine examination, but pathogenic Vibrio infection was similar to viral diarrhea. Conclusion: Infectious diarrhea presents different characteristics due to various symptoms which can provide a basis for clinical diagnosis.

Acute pancreatitis (AP) is a sudden inflammatory reaction, caused by the activation of pancreatic enzymes in the pancreas, and in severe cases can lead to systemic inflammation and multiple organ failure. Oxidative stress contributed to the further deterioration of inflammation and played an important role in AP development. Bilirubin has been found to exert antioxidative, anti-inflammatory, and anti-apoptotic effects in a series of diseases accompanied by a high level of oxidative stress. However, the therapeutic effects of bilirubin for AP management have not yet been demonstrated. Additionally, the poor solubility and potential toxicity of bilirubin also limit its application. Thus, we developed bilirubin encapsulated silk fibrin nanoparticles (BRSNPs) to study the protective effects and mechanisms of bilirubin nanomedicine for the treatment of AP. BRSNPs could selectively delivery to the inflammatory lesion of the pancreas and release bilirubin in an enzyme-responsive manner. In the model of AP caused by L-Arginine hyperstimulation, BRSNPs exerted strong therapeutic effects against AP by the reduction of oxidative stress, decreased expression of pro-inflammatory cytokines, and impaired recruitment of macrophages and neutrophils. The mechanism study indicated that BRSNPs protected acinar cells against extensive oxidative damage and inflammation through inhibiting NF-κB pathway and activating the Nrf2/HO-1 pathway. Collectively, for the first time, this study demonstrated that bilirubin nanomedicine, BRSNPs, are effective in alleviating experimental acute pancreatitis, and the mechanisms are associated with its inhibition of NF-κB regulated pro-inflammatory signaling and activation of Nrf2-regulated cytoprotective protein expression., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A unique polyketide cladosporactone A along with eight known compounds were isolated from the deep-sea-derived Cladosporium cladosporioides. The structure of cladosporactone A was established by spectroscopic analyses, and the absolute configuration was clarified by the theoretical ECD calculation. Cladosporactone A is the first member of polyketide with the 7-methylisochromen-3-one skeleton., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Islet transplantation has been considered the most promising therapeutic option with the potential to restore the physiological regulation of blood glucose concentrations in type 1 diabetes treatment. However, islets suffer from oxidative stress and nonspecific inflammation in the early stage of transplantation, which attributed to the leading cause of islet graft failure. Our previous study reported that bilirubin exerted antioxidative and anti-inflammatory effects on hypothermic preserved islets, which inspire us to utilize bilirubin to address the survival issue of grafted islets. However, the application of bilirubin for islet transplantation is limited by its poor solubility and fast clearance. In this study, we designed a supramolecular carrier (PLCD) that could improve the solubility of bilirubin and slowly release bilirubin to protect islets after cotransplantation. PLCD was synthesized by conjugating activated β-cyclodextrin (β-CD) to the side chain of ε-polylysine (PLL) and acted as a carrier to load bilirubin via host-guest interactions. The constructed bilirubin supramolecular system (PLCD-BR) significantly improved the solubility and prolonged the action time of bilirubin. In vitro results confirmed that PLCD-BR coculture substantially enhanced the resistance of islets to excessive oxidative stress and proinflammatory stimulation and maximumly maintained the islet function. In vivo, PLCD could prolong drug duration at the transplant site, and the localized released bilirubin could protect the islets from oxidative stress and suppress the production of inflammatory cytokines. Crucially, islet transplantation with PLCD-BR significantly extended the stable blood glucose time of diabetic mice and produced a faster glucose clearance compared to those cotransplanted with free bilirubin. Additionally, immunohistochemical analysis showed that PLCD-BR had superior antioxidative and anti-inflammatory abilities and beneficial effects on angiogenesis. These findings demonstrate that the PLCD-BR has great potentials to support successful islet transplantation.

Brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway is associated with ischemic heart diseases (IHD). 7,8-dihydroxyflavone (7,8-DHF), BDNF mimetic, is a potent agonist of TrkB. We aimed to investigate the effects and the underlying mechanisms of 7,8-DHF on cardiac ischemia. Myocardial ischemic mouse model was induced by ligation of left anterior descending coronary artery. 7,8-DHF (5 mg/kg) was administered intraperitoneally two days after ischemia for four weeks. Echocardiography, HE staining and transmission electron microscope were used to examine the function, histology and ultrastructure of the heart. H9c2 cells were treated with hydrogen peroxide (H 2 O 2 ), 7,8-DHF or TrkB inhibitor ANA-12. The effects of 7,8-DHF on cell viability, mitochondrial membrane potential (MMP) and mitochondrial superoxide generation were examined. Furthermore, mitochondrial fission and protein expression of mitochondrial dynamics (Mfn2 [mitofusin 2], OPA1 [optic atrophy 1], Drp1 [dynamin-related protein 1] and Fis-1 [fission 1]) was detected by mitotracker green staining and western blot, respectively. 7,8-DHF attenuated cardiac dysfunction and cardiomyocyte abnormality of myocardial ischemic mice. Moreover, 7,8-DHF increased cell viability and reduced cell death accompanied by improving MMP, inhibiting mitochondrial superoxide and preventing excessive mitochondrial fission of H 2 O 2 -treated H9c2 cells. The cytoprotective effects of 7,8-DHF were antagonized by ANA-12. Mechanistically, 7,8-DHF repressed OMA1-dependent conversion of L-OPA1 into S-OPA1, which was abolished by Akt inhibitor. In conclusion, 7,8-DHF protects against cardiac ischemic injury by inhibiting the proteolytic cleavage of OPA1. These findings provide a novel pharmacological effect of 7,8-DHF on mitochondrial dynamics and a new potential target for IHD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Combination of microalgae cultivation and piggery wastewater treatment has become a hot topic in recent years. Nutrient removal from aerated piggery wastewater (APW) by Desmodesmus sp. CHX1 and the optimization of cultivation conditions were investigated in this study. Results indicated that Desmodesmus sp. CHX1 showed an efficient growth in APW, with specific growth rate of 0.26-0.56 d -1 . The biomass yield based on nutrient consumption was 9.65 g biomass/g NH 4 -N and 209.15 g biomass/g total phosphorus (TP) respectively. Desmodesmus sp. CHX1 performed well in nutrient removal from APW, with ammonium nitrogen (NH 4 -N) and TP removal efficiency (RE) of 78.46% and 91.66% respectively after 7 days of culture. Nutrient removal process fitted the pseudo-first-order kinetic equations well, with removal rate (RR) constant of 0.24 d -1 for NH 4 -N and 0.28 d -1 for TP. The optimum conditions for nutrient removal from APW by Desmodesmus sp. CHX1 were light intensity of 150 μmol photons m -2  s -1 in the photoperiod for 24 h when the temperature was set at 35°C with alga cell inoculation concentration of 30%. The removal efficiencies of NH 4 -N and TP were 88.26% and 95.06% respectively under the optimal conditions after 7 days of culture. Our results can be a good reference for enhancement of microalga production and the nutrient RE and further extend the application of the large-scale piggery wastewater treatment under a controlled environment.

Objective: To investigate the molecular characteristics and intracellular growth ability of Legionella pneumophila (L. pneumophila) strains from 1989 to 2016 in Sichuan Province, China., Methods: Seventy-nine isolates of L. pneumophila were collected from environmental and clinical sources, including cooling towers, hot springs, bath water, fountains, and patients, and identified with 16S rRNA gene analysis and serum agglutination assay. The isolates were then typed by Sequence-Based Typing (SBT), and Genotyping of forty-two LP1 strains were analyzed by means of multiple-locus VNTR analysis with 8 loci (MLVA-8). All strains were further analyzed for two virulence genes: Legionella vir homologue (lvh) and repeats in structural toxin (rtxA). The intracellular growth ability of 33 selected isolates was determined by examining their interaction with J774 cells., Results: All isolates were identified to L. pneumophila including 11 serogroups, among which the main serogroup were LP1, accounting for 54.43%. Thirty-three different sequence types (STs) from five main clonal groups and five singletons were identified, along with 8 different MLVA patterns. Both the lvh and rtxA loci were found in all 79 strains. Thirty isolates showed high intracellular growth ability in J774 cells., Conclusion: L. pneumophila is a potential threat to public health, and effective control and prevention strategies are urgently needed., (Copyright © 2019 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Five new oxygenated sesquiterpenes, molestins A⁻D ( 1 , 3 ⁻ 5 ) and epi -gibberodione ( 2 ), three new cyclopentenone derivatives, ent -sinulolides C, D, and F ((+)- 9 ⁻(+)- 11 ), one new butenolide derivative, ent -sinulolide H ((+)- 13 ), and one new cembranolide, molestin E ( 14 ), together with 14 known related metabolites ( 6 ⁻ 8 , (⁻)- 9 ⁻(⁻)- 11 , (±)- 12 , (⁻)- 13 , 15 ⁻ 19 ) were isolated from the Paracel Islands soft coral Sinularia cf. molesta . The structures and absolute configurations were elucidated based on comprehensive spectroscopic analyses, quantum chemical calculations, and comparison with the literature data. Compound 5 is the first example of a norsesquiterpene with a de-isopropyl guaiane skeleton isolated from the genus Sinularia . Molestin E ( 14 ) exhibited cytotoxicities against HeLa and HCT-116 cell lines with IC 50 values of 5.26 and 8.37 μM, respectively. Compounds 4 , 5 , and 8 showed significant inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) with IC 50 values of 218, 344, and 1.24 μM, respectively.

Pediatric spinal ependymomas (SEPN) are important albeit uncommon malignant central nervous system tumors with limited treatment options. Our current knowledge about the underlying biology of these tumors is limited due to their rarity. To begin to elucidate molecular mechanisms that give rise to pediatric SEPN, we compared the transcriptomic landscape of SEPNs to that of intracranial ependymomas using genome-wide mRNA and microRNA (miRNA) expression profiling in primary tumour samples. We found that pediatric SEPNs are characterized by increased expression of genes involved in developmental processes, oxidative phosphorylation, cellular respiration, electron transport chain, and cofactor metabolic process. Next, we compared pediatric spinal and intracranial ependymomas with the same tumours in adults and found a relatively low number of genes in pediatric tumours that were shared with adult tumours (12.5%). In contrast to adult SEPN, down-regulated genes in pediatric SEPN were not enriched for position on chromosome 22. At the miRNA level, we found ten miRNAs that were perturbed in pediatric SEPN and we identified regulatory relationships between these miRNAs and their putative targets mRNAs using the integrative miRNA-mRNA network and predicted miRNA target analysis. These miRNAs include the oncomiR hsa-miR-10b and its family member hsa-miR-10a , both of which are upregulated and target chromatin modification genes that are down regulated in pediatric SEPN. The tumor suppressor, hsa-miR-124 , was down regulated in pediatric SEPN and it normally represses genes involved in cell-cell communication and metabolic processes. Together, our findings suggest that pediatric SEPN is characterized by a distinct transcriptional landscape from that of pediatric intracranial EPNs or adult tumors (both SEPNs and intracranial EPNs). Although confirmatory studies are needed, our study reveals novel molecular pathways that may drive tumorigenesis and could serve as biomarkers or rational therapeutic targets., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

Despite the fact that five kinds of uranium nitrides, i.e., uranium mononitrides (UN, R3̅m and Fm3̅m), a uranium dinitride (UN 2 , Fm3̅m), and uranium sesquinitrides (α-U 2 N 3 , Ia3̅; β-U 2 N 3 ,P3̅m1), have been confirmed, until now the phase relations are not well understood because of the puzzling nonstoichiometric issue. This work reinvestigated the crystallographic structures of these phases using cluster formula theory. The principal clusters (cuboctahedron with six squares and eight triangles) in these phases were determined. N atoms can occupy either six octahedral sites (square face centers) or eight tetrahedral sites (formed by a center atom and a triangle) in the principal cluster of 13 U atoms, resulting in these diversified phases and the nonstoichiometric issue. Also, phase transformations at certain temperatures and pressures (from CaF 2 -type UN 2 to Mn 2 O 3 -type U 2 N 3 , from Mn 2 O 3 -type U 2 N 3 to NaCl-type UN, and from NaCl-type UN to HgIn-type UN) were deduced by tracking the bond and angle changes of a simplified cluster [U-U 6 N 6 ]. This investigation provides an in-depth understanding of the phase relations in a U-N system.

A new piperidine alkaloid, microcosamine C (1), and one known compound, microcosamine A (2) were isolated from the leaves of Microcos paniculata. Structure elucidation was carried out using HR-ESI-MS, 1D and 2D NMR spectroscopic methods and by comparison with data reported in the literature. The absolute configuration at the C-3 hydroxy group of 1 was established by a Mosher esterification procedure. Both the isolates (1-2) were evaluated for cytotoxicity against four selected tumour cell lines and showed only weak activity against RAW 264.7 cell line.

Tritrophic interactions between Mythimna separata, its tachinid parasite Exorista civilis and the Cry1Ab were examined. Although 6th instar M. separata mortality increased with increasing Cry1Ab concentration, some tolerance was evident. Likewise, parasitization by E. civilis resulted in only 18% host mortality. However, combination of Cry1Ab and E. civilis parasitization resulted in a significant Cry1Ab dose-dependent increase in mortality over that of either alone, including a 50-56% synergistic increase in efficacy at the two concentrations tested. Pupal weight, adult emergence and lifetime fecundity of M. separata derived from larvae surviving both agents were negatively affected. The ability of E. civilis to parasitize and subsequently develop on the host was not adversely influenced by Cry1Ab. Instead, pupation rate increased significantly among host larvae fed 3.125 μg/g Cry1Ab diet. Overall, our results demonstrate that use of Cry1Ab to control M. separata not only is compatible with the use of the tachinid parasitoid, but that the two methods can act synergistically to manage this destructive pest, provide support for the safety of transgenic Cry1Ab Bt plants in China. This example of two independent pest management strategies acting synergistically against a difficult pest offers a new perspective of broad significance in striving for agricultural sustainability.

Objectives: Although uterine cancer is the fourth most common cause for cancer death in women worldwide, the molecular underpinnings of tumor progression remain poorly understood. The High Mobility Group A1 (HMGA1) gene is overexpressed in aggressive cancers and high levels portend adverse outcomes in diverse tumors. We previously reported that Hmga1a transgenic mice develop uterine tumors with complete penetrance. Because HMGA1 drives tumor progression by inducing MatrixMetalloproteinase (MMP) and other genes involved in invasion, we explored the HMGA1-MMP-2 pathway in uterine cancer., Methods: To investigate MMP-2 in uterine tumors driven by HMGA1, we used a genetic approach with mouse models. Next, we assessed HMGA1 and MMP-2 expression in primary human uterine tumors, including low-grade carcinomas (endometrial endometrioid) and more aggressive tumors (endometrial serous carcinomas, uterine carcinosarcomas/malignant mesodermal mixed tumors)., Results: Here, we report for the first time that uterine tumor growth is impaired in Hmga1a transgenic mice crossed on to an Mmp-2 deficient background. In human tumors, we discovered that HMGA1 is highest in aggressive carcinosarcomas and serous carcinomas, with lower levels in the more indolent endometrioid carcinomas. Moreover, HMGA1 and MMP-2 were positively correlated, but only in a subset of carcinosarcomas. HMGA1 also occupies the MMP-2 promoter in human carcinosarcoma cells., Conclusions: Together, our studies define a novel HMGA1-MMP-2 pathway involved in a subset of human carcinosarcomas and tumor progression in murine models. Our work also suggests that targeting HMGA1 could be effective adjuvant therapy for more aggressive uterine cancers and provides compelling data for further preclinical studies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To examine the skin whitening capabilities of shikimic acid pathway compounds and find the most effective molecule to be used as the active ingredient for skin whitening products., Materials and Methods: Skin whitening is the practice of using chemical substances to lighten skin tone by the lessening the concentration of melanin. The whitening efficacy of shikimic acid pathway compounds was evaluated. Eight compounds in the shikimic acid pathway were chosen for this study: benzoic acid, p-coumaric acid, vanillic acid, syringic acid, quinic acid, shikimic acid, orcinol monohydrate, and phenyl pyruvic acid. We measured the tyrosinase inhibitory capacity of the compounds in the animal model of zebrafish and also evaluated the compounds' anti-oxidant activities using the DPPH radical scavenging, and ABTS+ free radical scavenging tests. Compounds' cytotoxicity effects were also evaluated., Results: Amongst eight shikimic acid pathway compounds used in this study, shikimic acid was the most potent tyrosinase-inhibitor and the most efficient compound to be used as an active ingredient for skin whitening. Shikimic acid revealed a good radical scavenging activity (RAS) with low cell toxicity., Conclusions: Promising results obtained in this study may open a new window of opportunity to introduce another compound to be used in the skin-whiting cosmetics industry.

It has been reported that some single-nucleotide polymorphisms (SNPs) are associated with the risk of Parkinson's disease (PD), but whether a combination of these SNPs would have a stronger association with PD than any individual SNP is unknown. Sixteen SNPs located in the 8 genes and/or loci (SNCA, LRRK2, MAPT, GBA, HLA-DR, BST1, PARK16, and PARK17) were analyzed in a Chinese cohort consisting of 1061 well-characterized PD patients and 1066 control subjects from Central South of Mainland China. We found that Rep1, rs356165, and rs11931074 in SNCA gene; G2385R in LRRK2 gene; rs4698412 in BST1 gene; rs1564282 in PARK17; and L444P in GBA gene were associated with PD with adjustment of sex and age (p < 0.05) in the analysis of 16 variants. PD risk increased when Rep1 and rs11931074, G2385R, rs1564282, rs4698412; rs11931074 and G2385R, rs1564282, rs4698412; G2385R and rs1564282, rs4698412; and rs1564282 and rs4698412 were combined for the association analysis. In addition, PD risk increased cumulatively with the increasing number of variants (odds ratio for carrying 3 variants, 3.494). In summary, we confirmed that Rep1, rs356165, and rs11931074 in SNCA gene, G2385R in LRRK2 gene, rs4698412 in BST1 gene, rs1564282 in PARK17, and L444P in GBA gene have an independent and combined significant association with PD. SNPs in these 4 genes have a cumulative effect with PD., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Five mitochondrial protein-encoding genes (COX1, COX2, CytB, ND4 and ND5) from the wheat midge, Sitodiplosis mosellana (Diptera: Cecidomyiidae), were sequenced and compared with those of 3 other Cecidoidae species, Mayetiola destructor, Rhopalomyia pomum and Asphondylia rosetta. These genes shared similar AT content (74.0-80.1%) and base substitution bias in favour of transversions (68.87-79.72%) over transitions (20.28-37.04%). Substitution saturation analyses indicated fast saturation of transitional substitutions in COX2, CytB, ND4 and ND5, especially at the 3rd codon positions. Analysis of interspecific divergence among the 4 species showed that the sequence divergence rates (evolutionary rates) were in the order of ND4 = CytB > COX2 = ND5 > COX1. Intraspecific genetic polymorphism analysis within the field populations of S. mosellana indicated that ND4 had the highest genetic polymorphism and COX1 the lowest. Genetic variation patterns suggested that COX1 could be used as a molecular marker for phylogenetic analysis across a relatively wide taxonomic range in Cecidomyiidae, while COX2 and ND5 may be useful for estimating relationships at a subgenus level or among closely related species. With its high genetic polymorphism, ND4 was the molecular market most suitable for population genetics studies. These findings will be valuable for our further understanding and studies in evolutionary biology and population genetics for S. mosellana and other Cecidomyiidae insects.

The wheat midge, Sitodiplosis mosellana, is an important pest in Northern China. We tested the hypothesis that the population structure of this species arises during a range expansion over the past 30 years. This study used microsatellite and mitochondrial loci to conduct population genetic analysis of S. mosellana across its distribution range in China. We found strong genetic structure among the 16 studied populations, including two genetically distinct groups (the eastern and western groups), broadly consistent with the geography and habitat fragmentation. These results underline the importance of natural barriers in impeding dispersal and gene flow of S. mosellana populations. Low to moderate genetic diversity among the populations and moderate genetic differentiation (F ST = 0.117) between the two groups were also found. The populations in the western group had lower genetic diversity, higher genetic differentiation and lower gene flow (F ST = 0.116, Nm = 1.89) than those in the eastern group (F ST = 0.049, Nm = 4.91). Genetic distance between populations was positively and significantly correlated with geographic distance (r = 0.56, P<0.001). The population history of this species provided no evidence for population expansion or bottlenecks in any of these populations. Our data suggest that the distribution of genetic diversity, genetic differentiation and population structure of S. mosellana have resulted from a historical event, reflecting its adaptation to diverse habitats and forming two different gene pools. These results may be the outcome of a combination of restricted gene flow due to geographical and environmental factors, population history, random processes of genetic drift and individual dispersal patterns. Given the current risk status of this species in China, this study can offer useful information for forecasting outbreaks and designing effective pest management programs.

An analysis was made on the 16-year experimental data from the long term fertilization, experiment of maize on a yellow soil in Guizhou of Southwest China. Four treatments, i. e. , no fertilization (CK), chemical fertilization (165 kg N x hm(-2), 82.5 kg P2O5 x hm(-2), and 82.5 kg K2O x hm(-2), NPK), organic manure (30555 kg x hm(-2), M), and combined applicatioin of chemical fertilizers and organic manure (NPKM), were selected to analyze the variation trends of maize yield and fertilizer use efficiency on yellow soil under effects of different long term fertilization modes, aimed to provide references for evaluating and establishing long term fertilization mode and promote the sustainable development of crop production. Overall, the maize yield under long term fertilization had an increasing trend, with a large annual variation. Treatment NPKM had the best yield-increasing effect, with the maize yield increased by 4075.71 kg x hm(-2) and the increment being up to 139.2%. Long term fertilization increased the fertilizer utilization efficiency of maize. In treatment M, the nitrogen and phosphorus utilization rates were increased significantly by 35.4% and 18.8%, respectively. Treatment NPK had obvious effect in improving potassium utilization rate, with an increment of 20% and being far higher than that in treatments M (8.7%) and NPKM (9.2%). The results showed that long term fertilization, especially the combined application of chemical fertilizers and organic manure, was of great importance in increasing crop yield and fertilizer use efficiency.