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Taxonomy and phylogeny of poroid Hymenochaetaceae based on the most comprehensive phylogenetic analyses are presented. A phylogeny based on a combined dataset of ITS and nLSU sequences for accepted genera of Hymenochaetaceae was analyzed and multigene phylogenies for most species of ten large genera including Clotricia, Fomitiporella, Fomitiporia, Fulvifomes, Fuscoporia, Inonotus, Phylloporia, Porodaedalea, Sanghuangporus and Tropicoporus, were carried out. Based on samples from 37 countries of five continents, seven new genera, Meganotus, Neophellinus, Nothonotus, Pachynotus, Perenninotus, Pseudophylloporia and Rigidonotus, are introduced, 37 new species, Coltricia tibetica, Fomitiporella crassa, F. queenslandica, Fomitiporia eucalypti, F. gatesii, F. ovoidospora, Fulvifomes azonatus, F. caligoporus, F. costaricense, F. floridanus, F. jouzaii, F. nakasoneae, F. subindicus, Fuscoporia sinuosa, F. submurina, Inonotus subradiatus, I. vietnamensis, Neomensularia castanopsidis, Pachynotus punctatus, Phellinus cuspidatus, P. subellipsoideus, Phylloporia minutissima, P. tabernaemontanae, Porodaedalea occidentiamericana, P. orientoamericana, P. qilianensis, P. schrenkianae, Pseudophylloporia australiana, Sanghuangporus australianus, S. lagerstroemiae, Tropicoporus angustisulcatus, T. hainanicus, T. lineatus, T. minus, T. ravidus, T. substratificans and T. tenuis, are described, and 108 new combinations are proposed. In addition, one illegitimate name and two invalid names are renamed. The taxonomic relevance and limits of the new taxa are discussed. Photos and illustrations for 37 new species are presented, and a full description for each new species is given. Eventually, this study recognizes 672 species in 34 genera and provides a modern treatment of the poroid Hymenochaetaceae in the world. A key to the accepted poroid genera of Hymenochaetaceae is provided, and identification keys to the accepted species of 32 poroid genera worldwide are given. A synopsis description of each species is included in these keys.

The global "myopia boom" has raised significant international concerns. Despite a higher myopia prevalence in Asia, previous large-scale genome-wide association studies (GWASs) were mostly based on European descendants. Here, we report a GWAS of spherical equivalent (SE) in 1852 Chinese Han individuals with extreme SE from Guangzhou (631 -6.00D and 574 0.00D) and Wenzhou (593 -6.00D and 54 -1.75D), followed by a replication study in two independent cohorts with totaling 3538 East Asian individuals. The discovery GWAS and meta-analysis identify three novel loci, which show genome-wide significant associations with SE, including 1q25.2 FAM163A, 10p11.22 NRP1/PRAD3, and 10p11.21 ANKRD30A/MTRNR2L7, together explaining 3.34% of SE variance. 10p11.21 is successfully replicated. The allele frequencies of all three loci show significant differences between major continental groups (P 0.001). The SE reducing (more myopic) allele of rs10913877 (1q25.2 FAM163A) demonstrates the highest frequency in East Asians and much lower frequencies in Europeans and Africans (EAS = 0.60, EUR = 0.20, and AFR = 0.18). The gene-based analysis additionally identifies three novel genes associated with SE, including EI24, LHX5, and ARPP19. These results provide new insights into myopia pathogenesis and indicate the role of genetic heterogeneity in myopia epidemiology among different ethnicities.

Overexpression of various pro-inflammatory factors in microglial cells tends to induce neurodegenerative diseases, for which there is no effective therapy available. Aureonitol (1) and seven analogues, including six previously undescribed [elatumenol A-F (2-4, 6-8, respectively)], along with two new orsellinic acid esters [elatumone A and B (9 and 10)], were isolated from Chaetomium elatum. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including high-resolution mass spectra and one- and two-dimensional NMR, and absolute configurations determined by the Mosher method, dimolybdenum tetraacetate-induced circular dichroism, and theoretical calculations including electronic circular dichroism and NMR. Metabolites 3, 4, 7, and 8 exhibited antineuroinflammatory activity by attenuating the production of inflammatory mediators, such as nitric oxide, interleukin-6, interleukin-1β, tumor necrosis factor-α, and reactive oxygen species. Western blot results indicated 8 decreases the level of inducible nitric oxide synthase and cyclooxygenase-2 and suppresses the expression of Toll-like receptor 4 and nuclear factor kappa-B (NF-κB) as well as the phosphorylation of the inhibitor of NF-κB and p38 mitogen-activated protein kinases in lipopolysaccharide-activated BV-2 microglial cells.

In this review, we highlight the main insights that have been gathered from recent developments using large-scale genomics of fungal saprotrophs and symbiotrophs (including ectomycorrhizal and orchid and ericoid mycorrhizal fungi) inhabiting forest ecosystems. After assessing the goals and motivations underlying our approach, we explore our current understanding of the limits and future potential of using genomics to understand the ecological roles of these forest fungi. Comparative genomics unraveled the molecular machineries involved in lignocellulose decomposition in wood decayers, soil and litter saprotrophs, and mycorrhizal symbionts. They also showed that transitions from saprotrophy to mutualism entailed widespread losses of lignocellulose-degrading enzymes; diversification of novel, lineage-specific symbiosis-induced genes; and convergent evolution of genetic innovations that facilitate the accommodationof mutualistic symbionts within their plant hosts. We also identify the major questions that remain unanswered and propose new avenues of genome-based research to understand the role of soil fungi in sustainable forest ecosystems.

Aurora A kinase is a cell cycle regulator that is dysregulated in several different malignancies. Nevertheless, its regulatory mechanisms are still not fully understood. Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC. Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion. In this mechanism, USP3 leads to suppression of Aurora A ubiquitination, resulting less proteasome degradation. We constructed the deubiquitinated mimetic K143R of Aurora A and found that K143R significantly promoted the proliferation and invasion of ESCC cells and was not regulated by the deubiquitination of USP3. Moreover, Aurora A K143R potentiated the kinase activity of Aurora A in ESCC cells. Thus, our findings demonstrate that the tumorigenic feature of ESCC is in part mediated by USP3-facilitated deubiquitination of Aurora A.

RNF144A is a DNA damage-induced E3 ubiquitin ligase that targets proteins involved in genome instability for degradation, e.g., DNA-PKcs and BMI1. RNF144A is frequently mutated or epigenetically silenced in cancer, providing the rationale to evaluate RNF144A loss of function in tumorigenesis. Here we report that RNF144A-deficient mice are more prone to the development of bladder tumors upon carcinogen exposure. In addition to DNA-PKcs and BMI1, we identify the immune checkpoint protein PD-L1 as a novel degradation target of RNF144A, since these proteins are expressed at higher levels in Rnf144a KO tumors. RNF144A interacts with PD-L1 in the plasma membrane and intracellular vesicles and promotes poly-ubiquitination and degradation of PD-L1. Therefore, Rnf144a KO stabilizes PD-L1 and leads to a reduction of tumor-infiltrating CD8+ T cell populations in the BBN-induced bladder tumors. The bladder tumors developed in WT and Rnf144a KO mice primarily express CK5 and CK14, markers of basal cancer subtype, as expected in BBN-induced bladder tumors. Intriguingly, the Rnf144a KO tumors also express GATA3, a marker for the luminal subtype, suggesting that RNF144A loss of function promotes features of cellular differentiation. Such differentiation features in Rnf144a KO tumors likely result from a decrease of EGFR expression, consistent with the reported role of RNF144A in maintaining EGFR expression. In summary, for the first time our study demonstrates the in vivo tumor suppressor activity of RNF144A upon carcinogenic insult. Loss of RNF144A promotes the expression of DNA-PKcs, BMI1 and PD-L1, likely contributing to the carcinogen-induced bladder tumorigenesis.

Microglial activation and neuroinflammation induced by amyloid β (Aβ) play pivotal roles in Alzheimer's disease (AD) pathogenesis. Astragaloside IV (AS-IV) is one of the major active compounds of the traditional Chinese medicine Astmgali Radix. It has been reported that AS-IV could protect against Aβ-induced neuroinflammation and cognitive impairment, but the underlying mechanisms need to be further clarified. In this study, the therapeutic effects of AS-IV were investigated in an oligomeric Aβ (oAβ) induced AD mice model. The effects of AS-IV on microglial activation, neuronal damage and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression were further studied. Different doses of AS-IV were administered intragastrically once a day after intracerebroventricularly oAβ injection. Results of behavioral experiments including novel object recognition (NOR) test and Morris water maze (MWM) test revealed that AS-IV administration could significantly ameliorate oAβ-induced cognitive impairment in a dose dependent manner. Enzyme linked immunosorbent assay (ELISA) results showed that increased levels of reactive oxygen species (ROS), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and IL-6 in hippocampal tissues induced by oAβ injection were remarkably inhibited after AS-IV treatment. OAβ induced microglial activation and neuronal damage was significantly suppressed in AS-IV-treated mice brain, observed in immunohistochemistry results. Furthermore, oAβ upregulated protein expression of NADPH oxidase subunits gp91phox, p47phox, p22phox and p67phox were remarkably reduced by AS-IV in Western blotting assay. These results revealed that AS-IV could ameliorate oAβ-induced cognitive impairment, neuroinflammation and neuronal damage, which were possibly mediated by inhibition of microglial activation and down-regulation of NADPH oxidase protein expression. Our findings provide new insights of AS-IV for the treatment of neuroinflammation related diseases such as AD.

This study was carried out to analyse the growth performance, feed utilization, and antioxidant capacity of juvenile mud crab (Scylla paramamosain) reared in two conditions. Here, a new indoor polypropylene tank culture system and a traditional outdoor pond cage facility were used to perform feeding experiments on juvenile crabs. After eight weeks, the survival rate, weight gain, moulting rate and feed efficiency of crabs cultured in polypropylene tanks were markedly higher than those cultured in pond cages. Moreover, the activities of serum acid phosphatase (ACP) and alkaline phosphatase (ALP), and the antioxidant indices including glutathione peroxidase (GSH-PX), glutathione transferase (GST), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) in hepatopancreas were higher in crabs cultured in the polypropylene tank system than those in pond cages. Based on these results, compared with the traditional pond cages, the polypropylene tank culture system is more suitable for the short-term culture of mud crabs.

Bashir Lawal,1,2,* Yu-Cheng Kuo,3,4,* Maryam Rachmawati Sumitra,1,2 Alexander TH Wu,5– 8 Hsu-Shan Huang1,2,8– 10 1PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, 11031, Taiwan; 2Graduate Institute for Cancer Biology & Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan; 3Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan; 4School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan; 5The PhD Program of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan; 6Clinical Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, 11031, Taiwan; 7TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, 11031, Taiwan; 8Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, 11490, Taiwan; 9School of Pharmacy, National Defense Medical Center, Taipei, 11490, Taiwan; 10PhD Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei, 11031, Taiwan*These authors contributed equally to this workCorrespondence: Alexander TH Wu; Hsu-Shan Huang Email chaw1211@tmu.edu.tw; huanghs99@tmu.edu.twPurpose: Breast cancer is the most frequently diagnosed cancer globally, and the leading cause of cancer-associated mortality among women. The efficacy of most clinical chemotherapies is often limited by poor pharmacokinetics and the development of drug resistance by tumors. In a continuing effort to explore small molecules as alternative therapies, we herein evaluated the therapeutic potential of HH-N25, a novel nitrogen-substituted anthra[1,2-c][1,2,5]thiadiazole-6,11-dione derivative.Methods: We evaluated the in vivo pharmacokinetic properties and maximum tolerated dose (MTD) of HH-N25 in rats. We also characterized the compound for in vitro and in vivo anticancer activities and its inhibitory effects against DNA topoisomerases and hormonal signaling in breast cancer. Furthermore, we used molecular docking to analyse the ligand–receptor interactions between the compound and the targets.Results: The maximum serum concentration (Cmax), half-life (t1/2 beta), mean residence time (MRT), oral clearance (CL/f), and apparent volume of distribution (VD/f) of HH-N25 were 1446.67 ± 312.05 ng/mL, 4.51 ± 0.27 h, 2.56 ± 0.16 h, 8.32 ± 1.45 mL/kg/h, and 1.26 ± 0.15 mL/kg, respectively, after single-dose iv administration at 3 mg/kg body weight. HH-N25 had potent anticancer activity against a panel of human breast cancer cell lines with 50% inhibitory concentrations (IC50) ranging 0.045± 0.01∼ 4.21± 0.05 μM. The drug also demonstrated marked in vivo anticancer activity at a tolerated dose and prolonged the survival duration of mice without unacceptable toxicities based on body weight changes in human tumor xenograft models. In addition, HH-N25 exhibited a dose-dependent inhibition of topoisomerase I and ligand-mediated activities of progesterone and androgen receptors.Conclusion: HH-N25 represents a new molecular entity that selective suppressed TOP1 and hormonal signaling, and shows potent antitumor activities in human breast cancer cells in vitro and in vivo. HH-N25 thus represents a promising anticancer agent that warrants further preclinical and clinical exploration.Keywords: pharmacokinetic, anticancer activities, HH-N25, topoisomerase inhibition, hormonal signaling

Small heat shock proteins (sHSPs) function as molecular chaperones in multiple physiological processes and are active during thermal stress. sHSP expression is controlled by heat shock transcription factor (HSF); however, few studies have been conducted on HSF in agricultural pests. Liriomyza trifolii is an introduced insect pest of horticultural and vegetable crops in China. In this study, the master regulator, HSF1, was cloned and characterized from L. trifolii, and the expression levels of HSF1 and five sHSPs were studied during heat stress. HSF1 expression in L. trifolii generally decreased with rising temperatures, whereas expression of the five sHSPs showed an increasing trend that correlated with elevated temperatures. All five sHSPs and HSF1 showed an upward trend in expression with exposure to 40 ℃ without a recovery period. When a recovery period was incorporated after thermal stress, the expression patterns of HSF1 and sHSPs in L. trifolii exposed to 40 °C was significantly lower than expression with no recovery period. To elucidate potential interactions between HSF1 and sHSPs, double-stranded RNA was synthesized to knock down HSF1 in L. trifolii by RNA interference. The knockdown of HSF1 by RNAi decreased the survival rate and expression of HSP19.5, HSP20.8, and HSP21.3 during high-temperature stress. This study expands our understanding of HSF1-regulated gene expression in L. trifolii exposed to heat stress.

With the change to one scientific name for fungal taxa, generic names typified by species with sexual or asexual morph types are being evaluated to determine which names represent the same genus and thus compete for use. In this paper generic names of the Agaricomycotina (Basidiomycota) were evaluated to determine synonymy based on their type. Forty-seven sets of sexually and asexually typified names were determined to be congeneric and recommendations are made for which generic name to use. In most cases the principle of priority is followed. However, 16 generic names are recommended for use that do not have priority and thus need to be protected: Aleurocystis over Matula; Armillaria over Acurtis and Rhizomorpha; Asterophora over Ugola; Botryobasidium over Acladium, Allescheriella, Alysidium, Haplotrichum, Physospora, and Sporocephalium; Coprinellus over Ozonium; Coprinopsis over Rhacophyllus; Dendrocollybia over Sclerostilbum and Tilachlidiopsis; Diacanthodes over Bornetina; Echinoporia over Echinodia; Neolentinus over Digitellus; Postia over Ptychogaster; Riopa over Sporotrichum; Scytinostroma over Artocreas, Michenera, and Stereofomes; Tulasnella over Hormomyces; Typhula over Sclerotium; and Wolfiporia over Gemmularia and Pachyma. Nine species names are proposed for protection: Botryobasidium aureum, B. conspersum, B. croceum, B. simile, Pellicularia lembosporum (syn. B. lembosporum), Phanerochaete chrysosporium, Polyporus metamorphosus (syn. Riopa metamorphosa), Polyporus mylittae (syn. Laccocephalum mylittae), and Polyporus ptychogaster (syn. Postia ptychogaster). Two families are proposed for protection: Psathyrellaceae and Typhulaceae. Three new species names and 30 new combinations are established, and one lectotype is designated.

Samples of species close to Tremella fibulifera from China and Brazil are studied, and T. fibulifera is confirmed as a species complex including nine species. Five known species (T. cheejenii, T. fibulifera s.s., T. “neofibulifera”, T. lloydiae-candidae and T. olens) and four new species (T. australe, T. guangxiensis, T. latispora and T. subfibulifera) in the complex are recognized based on morphological characteristics, molecular evidence, and geographic distribution. Sequences of eight species of the complex were included in the phylogenetic analyses because T. olens lacks molecular data. The phylogenetic analyses were performed by a combined sequence dataset of the internal transcribed spacer (ITS) and the partial nuclear large subunit rDNA (nLSU), and a combined sequence dataset of the ITS, partial nLSU, the small subunit mitochondrial rRNA gene (mtSSU), the translation elongation factor 1-α (TEF1), the largest and second largest subunits of RNA polymerase II (RPB1 and RPB2). The eight species formed eight independent lineages with robust support in phylogenies based on both datasets. Illustrated description of the six species including Tremella fibulifera s.s., T. “neofibulifera” and four new species, and discussions with their related species, are provided. A table of the comparison of the important characteristics of nine species in the T. fibulifera complex and a key to the whitish species in Tremella s.s. are provided.

Lagotis brachystachya Maxim is an herb widely used in traditional Tibet medicine. Our previous study indicated that total extracts from Lagotis brachystachya could lower uric acid levels. This study aimed to further elucidate the active components (luteolin, luteoloside and apigenin) isolated from Lagotis brachystachya and the underlying mechanism in vitro and vivo. The results showed that treatment with luteolin and luteoloside reversed the reduction of organic anion transporter 1 (OAT1) levels, while apigenin attenuated the elevation of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) levels in uric acid-treated HK-2 cells, which were consistent with the finding in the kidney of potassium oxonate (PO)-induced mice. On the other hand, hepatic xanthine oxidase activity was inhibited by the components. In addition, all of these active components improved the morphology of the kidney in hyperuricemic mice. Moreover, molecular docking showed that luteolin, luteoloside and apigenin could bind TLR4 and NLRP3. Consistently, western blot showed that the components inhibited TLR4/MyD88/NLRP3 signaling. In conclusion, these results indicated that luteolin, luteoloside and apigenin could attenuate hyperuricemia by decreasing the production and increasing the excretion of uric acid, which were mediated by the inhibition of inflammatory signaling pathways.

Marine natural products play critical roles in the chemical defense of many marine organisms and are essential, reputable sources of successful drug leads. Sixty-seven 14-membered resorcylic acid lactone derivatives 3–27 and 30–71 of the natural product zeaenol (1) isolated from the marine-derived fungus Cochliobolus lunatus were semisynthesized by chlorination, acylation, esterification, and acetalization in one to three steps. The structures of these new derivatives were established by HRESIMS and NMR techniques. All the compounds (1–71) were evaluated for their antialgal and antiplasmodial activities. Among them, 14 compounds displayed antifouling activities against adhesion of the fouling diatoms. In particular, 9 and 34 exhibited strong and selective inhibitory effects against the diatoms Navicula laevissima and Navicula exigua (EC50 = 6.67 and 8.55 μmol/L), respectively, which were similar in efficacy to those of the positive control SeaNine 211 (EC50 = 2.90 and 9.74 μmol/L). More importantly, 38, 39, and 69–71 showed potent antiplasmodial activities against Plasmodium falciparum with IC50 values ranging from 3.54 to 9.72 μmol/L. Very interestingly, the five antiplasmodial derivatives displayed non-toxicity in the cytotoxicity assays and the zebrafish embryos model, thus, representing potential promising antiplasmodial drug agents. The preliminary structure–activity relationships indicated that biphenyl substituent at C-2, acetonide at positions C-5′ and C-6′, and tri- or tetra-substituted of acyl groups increased the antiplasmodial activity. Therefore, combining evaluation of chemical ecology with pharmacological models will be implemented as a systematic strategy, not only for environmentally friendly antifoulants but also for structurally novel drugs.

Haw-Ming Huang,1,2 Ping-Han Wu,3 Po-Chien Chou,4 Wen-Tien Hsiao,5 Hsin-Ta Wang,4 Hsin-Pei Chiang,3 Chi-Ming Lee,6 Shwu-Huey Wang,6 Yu-Cheng Hsiao2,7 1School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; 2Graduate Institute of Biomedical Optomechatronics, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 3Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 4School of Organic and Polymeric, National Taipei University of Technology, Taipei, Taiwan; 5Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan; 6Core Facility Center, Office of Research and Development, Taipei Medical University, Taipei, Taiwan; 7Cell Physiology and Molecular Image Research Center, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, TaiwanCorrespondence: Yu-Cheng Hsiao; Ping-Han WuTaipei Medical University, No. 250, Wu-Hsing Street, Taipei, 11031, TaiwanTel +886-291-937-9783Fax +886 2 27362295Email ychsiao@tmu.edu.tw; gahwclbjwph@gmail.comIntroduction: It has been reported that low-molecular-weight hyaluronic acid (LMWHA) exhibits a potentially beneficial effect on cancer therapy through targeting of CD44 receptors on tumor cell surfaces. However, its applicability towards tumor detection is still unclear. In this regard, LMWHA-conjugated iron (Fe3O4) nanoparticles (LMWHA-IONPs) were prepared in order to evaluate its application for enhancing the T2* weighted MRI imaging sensitivity for tumor detection.Methods: LMWHA and Fe3O4 NPs were produced using γ-ray irradiation and chemical co-precipitation methods, respectively. First, LMWHA-conjugated FITC was prepared to confirm the ability of LMWHA to target U87MG cells using fluorescence microscopy. The hydrodynamic size distribution and dispersion of the IONPs and prepared LMWHA-IONPs were analyzed using dynamic light scattering (DLS). In addition, cell viability assays were performed to examine the biocompatibility of LMWHA and LMWHA-IONPs toward U87MG human glioblastoma and NIH3T3 fibroblast cell lines. The ability of LMWHA-IONPs to target tumor cells was confirmed by detecting iron (Fe) ion content using the thiocyanate method. Finally, time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging and in vitro magnetic resonance imaging (MRI) were performed to confirm the contrast enhancement effect of LMWHA-IONPs.Results: Florescence analysis results showed that LMWHA-FITC successfully targeted the surfaces of both tested cell types. The ability of LMWHA to target U87MG cells was higher than for NIH3T3 cells. Cell viability experiments showed that the fabricated LMWHA-IONPs possessed good biocompatibility for both cell lines. After co-culturing test cells with the LMWHA-IONPs, detected Fe ion content in the U87MG cells was much higher than that of the NIH3T3 cells in both thiocyanate assays and TOF-SIMs images. Finally, the addition of LMWHA-IONPs to the U87MG cells resulted in an obvious improvement in T2* weighted MR image contrast compared to control NIH3T3 cells.Discussion: Overall, the present results suggest that LMWHA-IONPs fabricated in this study provide an effective MRI contrast agent for improving the diagnosis of early stage glioblastoma in MRI examinations.Keywords: hyaluronic acid, Fe3O4 nanoparticles, TOF-SIMS, MRI

A new species Tremella zhejiangensis is described from southeastern China based on phenotypic and molecular evidence. The species is characterized by soft gelatinous, yellowish brown to brownish orange, cerebriform basidioma when fresh, thin-walled, globose to subglobose or broadly ellipsoid basidia with a basal clamp connection, globose to subglobose basidiospores measuring 15.0–19.0 × 14.0–17.5 µm with obvious apiculus, and growth on rotten wood of Liquidambar formosana. The phylogeny of Tremella s.s. is constructed using methods of Maximum Parsimony, Maximum Likelihood and Bayesian Inference analyses based on the combined internal transcribed spacer regions (ITS) and the large subunit (nLSU) dataset. The results indicate that T. zhejiangensis forms a lineage independent of other species of Tremella s.s. An illustrated description of the new species is provided and related species are discussed.

An untargeted multi-omics study implicated the potential dysregulation of fatty acid, nucleotide, and energy metabolism in the brainstems of spontaneously hypertensive rats (SHRs). A further quantitative exploration of the alterations in the metabolic pathways is necessary for a deep understanding of the central nervous system in SHRs. Targeted metabolic profiling of 40 fatty acids (PeptideAtlas: PASS01671) and 32 metabolites of nucleotides and energy metabolism (PeptideAtlas: PASS01672) and parallel reaction monitoring analysis of 5 proteins (PeptideAtlas: PASS01673) were performed on the brainstems of SHRs (n = 8, 11 weeks old) and normotensive Wistar rats (n = 8, age-matched) using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem MS. The targeted profiling results of metabolites and proteins revealed decreased polyunsaturated fatty acid (PUFA) synthesis with a significant downregulation of cis-11,14-eicosadienoic acid, cis-13,16-docosadienoic acid, and docosatetraenoate and impaired PUFA oxidation with the accumulation of γ-linolenate induced by the significantly downregulated expression of 2,4-dienoyl-CoA reductase (p < 0.05). Dysregulated GTP and ATP metabolism was observed, with significantly decreased GDP and ADP (p < 0.05) correlated with reduced GTPases of guanine nucleotide-binding protein subunit beta-1 (GNB1), transforming protein RhoA (RHOA), and Rho-related GTP-binding protein RhoB (RHOB) in the brainstem of SHRs. In addition, protein-arginine deiminase type-2 was significantly reduced in the brainstems of SHRs (p < 0.05). The aberrant PUFA and energy metabolism might help to explain the alterations in the brainstem of SHRs. The findings on both metabolites and proteins could provide systemic insights into the pathology basis of altered PUFA and energy metabolism in hypertension, especially in the central nervous system.

A new gelatinous species, Calocera tibetica, is described from southwest China based on morphological and molecular evidence. It is characterized by stipitate, tough, gelatinous, dichotomously branched, dendroid or staghorn-like basidioma with blunt tips, subclavate to clavate basidia measuring 45.0–53.0 × 4.8–6.0 µm, and hyaline, oblong-ellipsoid to navicular, 3–4-septate mature basidiospores measuring 9.0–14.0 × 5.0–6.3 μm. In the phylogeny, the new species is closely related to C. viscosa and C. cornea based on the nITS + nLSU dataset, but C. viscosa has basidioma with sharp tips, pale yellow, 1-septate mature basidiospores; C. cornea has cylindrical, subulate, slightly branched basidioma, and sub-hyaline cylindrical to slightly curved-cylindrical, 1-septate mature basidiospores measuring 7–10 × 3–4.5 μm. The new species is unique by its 3–4-septate mature basidiospores among species of Calocera.

The niche variation hypothesis (NVH) predicts that populations with wider niches exhibit greater morphological variation through increased interindividual differences in both niche and morphology. In this study, we examined niche–trait relationships in three passerine species (Cyanoderma ruficeps, Sinosuthora webbiana, and Zosterops simplex). A total of 289 C. ruficeps from 7 sites, 259 S. webbiana from 8 sites, and 144 Z. simplex from 6 sites were sampled along an elevation gradient (0–2,700 m) in Taiwan from 2009 to 2017. We measured bill traits (length, width, and depth of bill) and body size traits (length of head, tarsus, and wing) of the birds, which were reduced to four principal components (bill PC1, bill PC2, body size PC1, and body size PC2). We collected feather tissues for stable carbon and nitrogen isotope analyses to quantify their isotope niche. We quantified interindividual differences in isotope space and trait space with four diversity metrics (divergence, dispersion, evenness, and uniqueness) and tested whether interindividual differences in isotope space and trait space are positively associated. We quantified population isotope niche width by Bayesian ellipse area and population morphological variation by variances of the PCs. The results showed that individual uniqueness in isotope niche and bill morphology (average closeness of individuals within the population isotope/trait space) were positively associated across three species. Furthermore, isotope niche width and bill PC1 (reflecting the size of bill) variation at population level were also positively associated across the three species, supporting the NVH. Of the three species, C. ruficeps and S. webbiana showed stronger support for the NVH than Z. simplex, possibly due to the latter having narrower elevational distribution and a more specialized, plant‐based diet. The diversity metrics represented different aspects of interindividual differences in niche/trait space, and for the passerines, individual uniqueness appeared to play an important role in their niche–trait dynamics., This study provided empirical evidence for the niche variation hypothesis in three passerine species (Cyanoderma ruficeps, Sinosuthora webbiana, and Zosterops simplex) in Taiwan. All three species showed positive associations between isotope niche width and bill size variation. Furthermore, all three species shared the same pattern that as individual birds occupied unique bill trait space within the population, they also tended to occupy unique isotope space, suggesting niche width expansion at population level through morphological differentiation at individual level.

Four new species of Bjerkandera, viz. B. ecuadorensis, B. fulgida, B. minispora, and B. resupinataspp. nov., are described from tropical America and Asia. B. ecuadorensis is characterised by dark grey to black pore surface, a monomitic hyphal system, hyaline to yellowish-brown generative hyphae, and ellipsoid basidiospores measuring 3.9–4.5 × 2.7–3 μm. B. fulgida is distinguished from the other species in the genus by clay buff to pale brown and shiny pore surface. B. minispora is characterised by white tomentose pore mouth and small basidiospores measuring 3.1–4.2 × 2–2.8 μm. B. resupinata is characterised by resupinate basidiomata, pinkish buff to pale brownish pore surface, and ellipsoid to broadly ellipsoid basidiospores measuring 4.5–6 × 3.2–4.1 µm. All these new species grow on angiosperm trunks or rotten wood, and cause a white rot. The closely related taxa to four new species are discussed. An identification key to the ten accepted species of Bjerkandera is provided, and a phylogeny comprising all known Bjerkandera species is provided.

Two novel natural products, beetleane A (1) and epicoane A (2), were obtained from the metabolites of an endophytic Epicoccum nigrum. Compound 1 has a unique beetlelike structure that is constructed by the fusion and further fold of an unusual [5.5.5.6]trioxafenestrane with a cycloheptane ring. Compound 2 possesses a compact cagelike structure with a unique 6/5/5/5/6/6/5 heptacyclic ring system. Both 1 and 2 showed strong antiliver fibrosis activity in vitro.

The alternating direction method of multipliers (ADMM) has been adapted for decoding low-density parity-check (LDPC) codes over intersymbol interference (ISI) channels in order to reduce the complexity of the traditional Turbo equalization (TE) method. However, the error rate performance of ADMM decoding may be degraded in certain ISI channels when compared with the TE at high signal-to-noise ratio regions. In order to address the problem, we derive a novel ADMM-based decoding method, called $l_2$ -box ADMM decoding, for LDPC codes over ISI channels. By introducing suitable penalty functions to $l_2$ -box ADMM decoding, we present an enhanced method, called $l_2$ -box ADMM penalized decoding, to further improve the performance. Simulation results on several ISI channels indicate that the proposed $l_2$ -box ADMM penalized decoding can achieve better error rate performances compared with the TE and the existing ADMM penalized decoding methods, especially for ISI channels with long memory, while maintaining the low-complexity advantage of the ADMM penalized decoding.

BACKGROUND Osimertinib is the recommended first-line treatment for adult patients with epidermal growth factor receptor (EGFR) mutation positive advanced or metastatic non-small cell lung cancer (NSCLC). However, primary or acquired resistance to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) seems inevitable, and when drug-resistance occurs during treatment with osimertinib, the standard of care is to discontinue the TKI. CASE SUMMARY A 57-year-old female patient with lung adenocarcinoma presented with an irritating cough accompanied by chest distress of one month duration. An enhanced head magnetic resonance imaging scan showed brain metastases. An EGFR mutation (exon 21 L858R) was detected in pleural fluid. The patient was treated with oral osimertinib (80 mg once daily) from January 2018 but developed progressive disease on December 2018. She was then successfully treated with re-challenge and tri-challenge with osimertinib (80 mg once daily) by resensitization chemotherapy twice after the occurrence of drug-resistance to osimertinib, and to date has survived for 31 mo. CONCLUSION This case may provide some selective therapeutic options for NSCLC patients with acquired drug-resistance who were previously controlled on osimertinib treatment.

Muscle regeneration after damage or during myopathies requires a fine cooperation between myoblast proliferation and myogenic differentiation. A growing body of evidence suggests that microRNAs play critical roles in myocyte proliferation and differentiation transcriptionally. However, the molecular mechanisms underlying the orchestration are not fully understood. Here, we showed that miR-130b is able to repress myoblast proliferation and promote myogenic differentiation via targeting Sp1 transcription factor. Importantly, overexpression of miR-130b is capable of improving the recovery of damaged muscle in a freeze injury model. Moreover, miR-130b expression is declined in the muscle of muscular dystrophy patients. Thus, these results indicated that miR-130b may play a role in skeletal muscle regeneration and myopathy progression. Together, our findings suggest that the miR-130b/Sp1 axis may serve as a potential therapeutic target for the treatment of patients with muscle damage or severe myopathies.

A new poroid wood-inhabiting fungus in the family Steccherinaceae, Steccherinum fragile sp. nov., is described and illustrated from China based on morphological and molecular evidence. The species was collected in Yunnan Province, growing on the ground and undersides of rotten angiosperm wood. S. fragile is characterized by an annual growth habit, resupinate basidiocarps with salmon to peach pores when fresh becoming cinnamon buff to pinkish buff upon drying, a thin margin with distinct rhizomorphs, a monomitic hyphal system, generative hyphae thin- to distinctly thick-walled with simple septa, neither amyloid nor cyanophilous. The phylogenetic analysis based on ITS + nLSU rDNA sequences shows that the new species belongs to Steccherinum, forming a monophyletic lineage with strong support (100% BS, 100% BP, 1.00 BPP). In addition, a new combination, S. subcollabens, is also proposed based on examination of its type material and phylogenetic analysis. Phylogenetically, Steccherinum fragile is closely related to S. amapaense and groups with S. subcollabens, S. formosanum and S. collabens. Both morphological and molecular characters confirm the placement of the new species and combination in Steccherinum.

Thorough understanding of the role of CD4 T cells in immunity can be greatly assisted by the study of responses to defined specificities. This requires knowledge of Plasmodium-derived immunogenic epitopes, of which only a few have been identified, especially for the mouse C57BL/6 background. We recently developed a TCR transgenic mouse line, termed PbT-II, that produces CD4+ T cells specific for an MHC class II (I-Ab)-restricted Plasmodium epitope and is responsive to both sporozoites and blood-stage P. berghei. Here, we identify a peptide within the P. berghei heat shock protein 90 as the cognate epitope recognised by PbT-II cells. We show that C57BL/6 mice infected with P. berghei blood-stage induce an endogenous CD4 T cell response specific for this epitope, indicating cells of similar specificity to PbT-II cells are present in the naive repertoire. Adoptive transfer of in vitro activated TH1-, or particularly TH2-polarised PbT-II cells improved control of P. berghei parasitemia in C57BL/6 mice and drastically reduced the onset of experimental cerebral malaria. Our results identify a versatile, potentially protective MHC-II restricted epitope useful for exploration of CD4 T cell-mediated immunity and vaccination strategies against malaria.

Aims: Pathological cardiac fibrosis and hypertrophy are common features of left ventricular remodeling that often progress to heart failure (HF). Endothelial cells (ECs) are the most abundant non-myocyte cells in adult mouse heart. Simvastatin, a strong inducer of Krüppel-like Factor 2 (Klf2) in ECs, ameliorates pressure overload induced maladaptive cardiac remodeling and dysfunction. This study aims to explore the detailed molecular mechanisms of the anti-remodeling effects of simvastatin. Methods and Results: RGD-magnetic-nanoparticles were used to endothelial specific delivery of siRNA and we found absence of simvastatin's protective effect on pressure overload induced maladaptive cardiac remodeling and dysfunction after in vivo inhibition of EC-Klf2. Mechanism studies showed that EC-Klf2 inhibition reversed the simvastatin-mediated reduction of fibroblast proliferation and myofibroblast formation, as well as cardiomyocyte size and cardiac hypertrophic genes, which suggested that EC-Klf2 might mediate the anti-fibrotic and anti-hypertrophy effects of simvastatin. Similar effects were observed after Klf2 inhibition in cultured ECs. Moreover, Klf2 regulated its direct target gene TGFβ1 in ECs and mediated the protective effects of simvastatin, and inhibition of EC-Klf2 increased the expression of EC-TGFβ1 leading to simvastatin losing its protective effects. Also, EC-Klf2 was found to regulate EC-Foxp1 and loss of EC-Foxp1 attenuated the protective effects of simvastatin similar to EC-Klf2 inhibition. Conclusions: We conclude that cardiac microvasculature ECs are important in the modulation of pressure overload induced maladaptive cardiac remodeling and dysfunction, and the endothelial Klf2-TGFβ1 or Klf2-Foxp1-TGFβ1 pathway mediates the preventive effects of simvastatin. This study demonstrates a novel mechanism of the non-cholesterol lowering effects of simvastatin for HF prevention.

Mesenchymal stem cells (MSCs) can be obtained from almost all tissues and present promising therapeutic effects for metabolic diseases. Human adipose-derived MSCs (hASCs) have recently been widely studied due to their easy access and low immunity. Thus, we intended to figure out the effects and potential mechanism of hASCs on obesity in high-fat-diet (HFD)-induced obese mice. Following 16 weeks of being fed HFD, hASCs were intravenously injected. Two weeks later, body weight, body composition, and energy expenditure were evaluated. Additionally, the phenotypes of macrophages infiltrating adipose tissue were analyzed. The results revealed that hASCs administration significantly reduced adipose tissue weight, adipocyte size, and fat mass and exerted beneficial effects in serum lipid profile. This anti-obesity effect was mediated by the increased O2 consumption, CO2 production, and energy expenditure, which was further evidenced by the upregulation of uncoupling protein-1 (UCP-1) and metabolism-associated genes. Furthermore, hASCs infusion increased the amount of alternatively activated (M2) macrophages in adipose tissue, and the expression of pro-inflammatory cytokines-related genes was reduced. Taken together, these results indicated that hASCs suppressed obesity by increasing UCP-1 expression and enhancing energy expenditure, and this effect might be due to the increased M2 macrophages.

Based on morphological characteristics and molecular evidence, two new species of Panellus, P. bambusicola and P. yunnanensis, are described and illustrated from Yunnan Province, southwestern China. Both species are characterized by white and gelatinous basidiocarps, poroid hymenophore which is concolorous with the pileal surface, a monomitic hyphal system with slightly thick-walled tramal hyphae. P. bambusicola has oblong ellipsoid to ellipsoid basidiospores measuring 6–7.2 × 3–3.8 μm, whereas P. yunnanensis has ellipsoid to broadly ellipsoid basidiospores measuring 6.5–8.5 × 3.8–4.5 μm. In addition, samples of P. bambusicola and P. yunnanensis formed two distinct phylogenetic lineages based on the internal transcribed spacer regions (ITS) and nuclear large subunit ribosomal RNA gene regions (nLSU) sequences.

Twelve new compounds, aspergorakhins A–L (1–12) coupled with one known xanthone leptosphaerin D (13), were isolated from the extract of soil-derived fungus Aspergillus gorakhpurensis F07ZB1707. Their structures were elucidated by spectroscopic data analysis including UV, IR, NMR, and HRESIMS. The absolute configurations of 5 and 8–11 were identified using ECD and OR calculations. All compounds were tested by enzyme inhibitory activity assay in vitro. Aspergorakhin A (1) showed selective activities against PTP1B and SHP1 over TCPTP with IC50 values 0.57, 1.19, and 22.97 μM, respectively. Compounds 1 and 2 exhibited modest cytotoxicity against tumor cell lines A549, HeLa, Bel-7402, and SMMC-7721 with IC50 values in the range of 6.75–83.4 μM.

Targeting EGFR, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), brings lights to the treatment of non-small cell lung cancer (NSCLC). Although T790M mutation responded as one of the main reasons of acquired resistance, still 15% of the resistance patients can't be explained by the known mechanisms. The purpose of this research was to identify some new mechanisms of gefitinib acquired resistance, and to predict small molecules drugs which may reverse drug resistance by integrated bioinformatics analysis. The GSE34228 data package containing the microarray data of acquired gefitinib-resistant cell line (PC9GR) and gefitinib-sensitive cell line (PC9) from the GEO database were downloaded, and gene co-expression networks by weighted gene co-expression network analysis (WGCNA) were constructed to identified key modules and key genes related to gefitinib resistance. Furthermore, the significantly differentially expressed genes (DEGs) between the two cell types were screened out, and a protein-protein interaction (PPI) network to obtain the key genes of DEGs was accordingly constructed. Through the above two methods, 4 hub genes, PI3, S100A8, AXL and PNPLA4 were mined as the most relevant to gefitinib resistance. Among them, PI3, S100A8 were down-regulated in PC9GR cell samples, while AXL, PNPLA4 were up-regulated. The gene set enrichment analysis (GSEA) for single gene showed that the four hub genes were mainly correlated with cell proliferation and cycle. Besides, small molecule drugs with the potential to overcome resistance, such as Emetine and cephaeline, were screened by CMap database. Consistent with this, in vitro experiments results have shown that emetine and cephaeline can increase the sensitivity of drug-resistant cells to gefitinib, and the mechanism may be related to the regulation of PI3 and S100A8. In conclusion, 4 hub genes were found to be related to the occurrence of gefitinib resistance in non-small cell lung cancer, and several small molecule drugs were screened out as potential therapeutic agents to overcome gefitinib resistance, which may lead a new way for the treatment of NSCLC of acquired resistance to gefitinib.

RNA molecules contain many chemical modifications that can regulate a variety of biological processes. Messenger RNA (mRNA) molecules are critical components in the central dogma of molecular biology. The discovery of reversible chemical modifications in eukaryotic mRNA brings forward a new research field in RNA modification-mediated regulation of gene expression. The modifications in mRNA generally exist in low abundance. The use of highly pure mRNA is critical for the confident identification of new modifications as well as for the accurate quantification of existing modifications in mRNA. In addition, isolation of highly pure mRNA is the first step in many biological research studies. Therefore, the methods for isolating highly pure mRNA are important for mRNA-based downstream studies. A variety of methods for isolating mRNA have been developed in the past few decades and new methods continuously emerge. This review focuses on the methodologies and protocols for isolating mRNA populations. In addition, we discuss the advantages and limitations of these methods. We hope this paper will provide a general view of mRNA isolation strategies and facilitate studies that involve mRNA modifications and functions.

The assembly of DNA with metal-complex cofactors can form promising biocatalysts for asymmetric reactions, although catalytic performance is typically limited by low enantioselectivities and stereo-control remains a challenge. Here, we engineer G-quadruplex-based DNA biocatalysts for an asymmetric cyclopropanation reaction, achieving enantiomeric excess (eetrans) values of up to +91% with controllable stereoinversion, where the enantioselectivity switches to −72% eetrans through modification of the Fe-porphyrin cofactor. Complementary circular dichroism, nuclear magnetic resonance, and fluorescence titration experiments show that the porphyrin ligand of the cofactor participates in the regulation of the catalytic enantioselectivity via a synergetic effect with DNA residues at the active site. These findings underline the important role of cofactor modification in DNA catalysis and thus pave the way for the rational engineering of DNA-based biocatalysts.

Based on morphological characteristics and molecular phylogenetic analysis using nuc rDNA ITS1-5.8S-ITS2 and 28S rDNA sequences, two new species of Physisporinus, Physisporinus castanopsidis sp. nov. and Physisporinus roseus sp. nov. are described from Yunnan Province, Southwest China. Physisporinus castanopsidis is characterised by resupinate, snow white and waxy basidiocarps which become pale brown when bruised, abundant hymenial cystidia and cystidia-like hyphae at dissepiment edge, generative hyphae with swollen tips, distinctly ovoid basidiospores measuring 4.8–5.6 × 3.6–4.2 μm and growing on rotten wood or roots of Castanopsis. Physisporinus roseus is characterised by perennial, resupinate and thick basidiomata with rose fresh pores which becoming vinaceous grey up on drying, a distinct context layer present among tube layers, abundant clavate, smooth cystidia and subglobose basidiospores measuring 3.5–4.1 × 3.1–3.8 μm.

Background Tumor-targeted nanoparticles hold great promise as new tools for therapy of liquid cancers. Furthermore, the therapeutic efficacy of nanoparticles can be improved by enhancing the cancer cellular internalization. Methods In this study, we developed a humanized bispecific antibody (BsAbs: CD20 Ab-mPEG scFv) which retains the clinical anti-CD20 whole antibody (Ofatumumab) and is fused with an anti-mPEG single chain antibody (scFv) that can target the systemic liquid tumor cells. This combination achieves the therapeutic function and simultaneously “grabs” Lipo-Dox® (PEGylated liposomal doxorubicin, PLD) to enhance the cellular internalization and anticancer activity of PLD. Results We successfully constructed the CD20 Ab-mPEG scFv and proved that CD20 Ab-mPEG scFv can target CD20-expressing Raji cells and simultaneously grab PEGylated liposomal DiD increasing the internalization ability up to 60% in 24 h. We further showed that the combination of CD20 Ab-mPEG scFv and PLD successfully led to a ninefold increase in tumor cytotoxicity (LC50: 0.38 nM) compared to the CD20 Ab-DNS scFv and PLD (lC50: 3.45 nM) in vitro. Importantly, a combination of CD20 Ab-mPEG scFv and PLD had greater anti-liquid tumor efficacy (P = 0.0005) in Raji-bearing mice than CD20 Ab-DNS scFv and PLD. Conclusion Our results indicate that this “double-attack” strategy using CD20 Ab-mPEG scFv and PLD can retain the tumor targeting (first attack) and confer PLD tumor-selectivity (second attack) to enhance PLD internalization and improve therapeutic efficacy in liquid tumors.

Liriomyza spp. (Diptera: Agromyzidae) represent a group of economically-significant highly polyphagous pests of plants grown in field and greenhouse conditions. Liriomyza spp. share similar biological and morphological characteristics, and complex interspecific interactions have been documented among these species in various geographical regions. Where the displacement of one of these species by the other has been studied, no unique mechanisms have been identified as causing it. The impact of competitive factors (such as, insecticide tolerance, thermotolerance, and adaptability to cropping systems) may be unique to specific geographic regions of Liriomyza spp., but more research is needed to confirm these hypotheses. In this study, RNA-seq was used to determine the transcriptomes of three closely-related leafminers, e.g. L. sativae, L. trifolii, and L. huidobrensis. Over 20 Gb of clean reads were generated and assembled into unique transcriptomes, and 38,747 unigenes were annotated in different databases. In pairwise comparisons, L. trifolii and L. sativae had more up-regulated genes than L. huidobrensis. With respect to common differentially-expressed genes (Co-DEGs), the three leafminers exhibited distinct groups of highly-expressed gene clusters. When genes related to competitive factors were compared, expression patterns in L. trifolii and L. sativae were more closely related to each other than to L. huidobrensis. The data suggest that DEGs involved in competitive factors may play a key role in competition and displacement of leafminers. The divergent genes identified in this study will be valuable in revealing possible mechanisms of invasion, displacement and interspecific competition in Liriomyza spp.

European catfish (Silurus glanis) is a commercially important freshwater fish originating from Eastern Europe. The objective of this study was to examine the short-term storage of its eggs especially in relation to maintaining a low level of malformation in newly hatched fry. The eggs from freshly spawned individuals were stored separately in cell incubators at 17 and 22 °C under aerobic conditions. Changes in fertilization, hatching, and malformation were examined in eggs stored at 1, 3, 5, and 7 h post-stripping. The sperm used for fertilization showed very good motility rates (84–90%) and curvilinear velocity (110–125 μm/s), and straight-line velocity did not drop below 77 μm/s. For all females, a temperature of 17 °C was better than 22 °C for egg storage in vitro. Egg fertilization and total hatching decreased rapidly after 7 h storage at 17 °C. The storage time of eggs in vitro to fertilization should therefore not exceed 5 h at 17 °C. In all females, there was no difference in the total number of eggs hatching between 1 and 3 h of egg storage at 17 °C. The storage time of eggs did not correlate with the level of malformations of the fry. However, the level of hatching and malformations was clearly affected by the storage temperature of eggs when it was > 17 °C. Analysis showed that the storage time of eggs, temperature of storage, and individual females had a significant influence on fertilization and total hatching rates. Regression analysis confirmed a low correlation of fertilization and hatching rates with storage time of eggs.

Fuscoporia caymanensis sp. nov. is described from tropical America. It is characterized by perennial, extensive, resupinate to indistinctly effused-reflexed basidiomata; a very thin to almost absent subiculum; multi-layered tubes with a black line between each layer; a dimitic hyphal system with skeletal hyphae occasionally septate; absence of mycelial setae and cystidioles; abundant hymenial setae, 40–55 × 5–7 μm; urniform basidia, and cylindrical basidiospores 4.5–5 × 2–2.4 µm. It was found growing on fallen rotten angiosperm trunks in tropical America. Phylogenetically, it is related to Fuscoporia viticola and F. palomari, but the latter two species have longer basidiospores (7–9 × 1.5–2 µm in F. viticola and 8–10 × 2.7–3.5 μm in F. palomari), and occur in temperate regions.

Two new phenolic glycosides 7R,8R-threo-4,7,9,9'-tetrahydroxy-3-methoxy-8-O-4'-neolignan-3'-O-(3''-α-L-arabinofuranosyl)-β-D-glucopyranoside. (1), 4-(4'-hydroxyphenyl)-2-butanone-4''-O-(6-β-D-xylosyl)-β-D-glucopyranoside (2), along with two known related analogues 7R,8R-threo-4,7,9,9'-tetrahydroxy-3-methoxy-8-O-4'-neolignan-3'-O-β-D-glucopyranoside (3), 4-(4'-hydroxyphenyl)-2-butanone-4'-O-β-D-glucopyranoside (4) were obtained from the roots of Sanguisorba officinalis. Combined with acid hydrolysis derivatization, the absolute configurations of these new compounds were elucidated by comprehensive analyses of spectroscopic data including nuclear magnetic resonance (NMR), electrospray ionization high resolution mass (HRESIMS) as well as circular dichroism (CD). Compounds 1-4 exhibited anti-inflammatory properties in vitro by attenuating the production of inflammatory mediators, such as nitric oxide (NO) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).

Background The expression of Kelch-like protein 18 (KLHL18) in non-small cell lung cancer (NSCLC) is lower than that in normal lung tissue according to the Gene Expression Profiling Interactive Analysis database. KLHL18 is a BTB domain protein and binds cullin 3 (CUL3). However, whether this complex participates in ubiquitination-mediated protein degradation in NSCLC is unclear. Therefore, we aimed to investigate the role of KLHL18 in human NSCLC cells. Results We found that KLHL18 is downregulated in cancer cells and is associated with poor prognosis. Further, its expression was significantly associated with tumor node metastasis (TNM) stage, lymph node metastasis, and tumor size. In vitro analysis of NSCLC cells showed that overexpressing KLHL18 inhibited cell proliferation, migration, and invasion. We found that the tumor-inhibitory effect of the KLHL18 protein was achieved by promoting the ubiquitination and degradation of phosphatidylinositol 3-kinase (PI3K) p85α and inhibiting the expression of PD-L1 protein, ultimately preventing tumor cell immune escape. Conclusions Our results identified the tumor-suppressive mechanism of KLHL18 and suggested that it is closely related to NSCLC occurrence and development. Further investigation of the underlying mechanism may provide new targets for NSCLC treatment.

Background Cardiac troponins are important markers for diagnosis of acute myocardial infarction (AMI) in general population; however, chronically-elevated troponins levels are often seen in patients with renal insufficiency, which reduce their diagnostic accuracy. The aim of our study was to access the diagnostic values of initial high-sensitive cardiac troponin T (hs-cTnT) and relative change of hs-cTnT for AMI in patients with and without renal insufficiency. Methods Cardiac care unit patients with elevated hs-cTnT levels in 2017–2018 were enrolled. Receiver operating characteristic (ROC) curves were used to evaluate initial hs-cTnT levels and relative changes after 3 h of enrollment for diagnosis of AMI in patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (low), and eGFR ≥ 60 mL/min/1.73 m2 (normal). Results Of 359 patients, 240 patients had low eGFR, and 119 patients had normal eGFR. The area under the ROC curve (AUC) for the initial hs-cTnT levels was 0.58 (95% CI, 0.5–0.65, p = 0.053) among patients with low eGFR and 0.54 (95% CI, 0.4–0.67, p = 0.612) among patients with normal eGFR. AUCs for relative changes of hs-cTnT were 0.82 (95% CI, 0.76–0.88, p

Two new C29 steroids, xidaosterols A (1) and B (2), characterised by a common unusual α-keto-enol functionality bearing A-ring, together with three related known ones (3–5), were isolated from the ...

Klebsiella pneumoniae causes pneumonia and liver abscesses in humans worldwide and contains virulence factor capsular polysaccharides and lipopolysaccharides linked to the cell wall. Although capsular polysaccharides are good antigens for vaccine production and capsular oligosaccharides conjugate vaccines are proven effective against infections caused by encapsulated pathogens, there is still no Klebsiella pneumoniae vaccine available. One obstacle is that the capsular polysaccharide of a dominated Klebsiella pneumoniae serotype K2 is difficult to synthesize chemically due to the three 1,2-cis linkages in its structure. In this study, we successfully synthesized K2 capsular polysaccharides from tetra- to octasaccharides in highly a stereoselective manner. Subsequently, three synthesized glycans were conjugated to DT protein to provide glycoconjugate vaccine candidates (DT-Hexa, DT-Hepta, and DT-Octa) that were used in in vivo immunization experiments in mice. The results of immunized studies showed all three glycoconjugates elicited antibodies that recognized all of the synthetic glycans at 1:200-fold dilution. Particularly, the DT-Hepta conjugate elicited a higher level of antibodies that can recognize longer glycan (octasaccharide) even at 1:12800-fold dilution and exhibited good bactericidal activity. Our results concluded that heptasaccharide is the minimal epitope and a potential candidate for the vaccine against the K2 sero group of Klebsiella pneumoniae.

Cordycepin is the major bioactive component extracted from Cordyceps militaris. In recent years, cordycepin has received increasing attention owing to its multiple pharmacological activities. This study reviews recent researches on the anti-inflammatory effects and the related activities of cordycepin. The results from our review indicate that cordycepin exerts protective effects against inflammatory injury for many diseases including acute lung injury (ALI), asthma, rheumatoid arthritis, Parkinson's disease (PD), hepatitis, atherosclerosis, and atopic dermatitis. Cordycepin regulates the NF-κB, RIP2/Caspase-1, Akt/GSK-3β/p70S6K, TGF-β/Smads, and Nrf2/HO-1 signaling pathways among others. Several studies focusing on cordycepin derivatives were reviewed and found to down metabolic velocity of cordycepin and increase its bioavailability. Moreover, cordycepin enhanced immunity, inhibited the proliferation of viral RNA, and suppressed cytokine storms, thereby suggesting its potential to treat COVID-19 and other viral infections. From the collected and reviewed information, this article provides the theoretical basis for the clinical applications of cordycepin and discusses the path for future studies focusing on expanding the medicinal use of cordycepin. Taken together, cordycepin and its analogs show great potential as the next new class of anti-inflammatory agents.

Improvement of sperm quality with low motility by storage could ensure higher success of fertilization and maintain higher genetic diversity, especially for sturgeons, which as endangered species have limited broodstock and gametes. Sperm was collected from mature male sterlet Acipenser ruthenus and motility was evaluated using the CASA system; samples were categorized as GS 'good sperm' (80%) or BS 'bad sperm' (20%). Samples from both groups were incubated with seminal plasma from good- (GSP) and bad-quality sperm (BSP), respectively for 15 min, 6 h, 24 h and 96 h at 4 °C. Motility of BS incubated in GSP increased after different storage times compared to BS incubated in BSP, while the motility and velocity of GS incubated in BSP decreased compared to GS incubated in GSP. Fertilization rates were evaluated with samples stored for 15 min and 6 h post-stripping; fertilization and hatching rate of BS after incubation in GSP increased significantly compared to the BS incubated in BSP. Inorganic ion (Na

Background: We found that Taiwanese adults carrying genotypes of UDP-glucuronosyltransferase (UGT) 1A1 with enzyme activity ≤40% of normal were at high risk for developing Gilbert's syndrome. However, the relationship between UGT1A1 activity and neonatal hyperbilirubinemia has never been evaluated for Taiwanese. Methods: We enrolled 141 hyperbilirubinemic neonates partially fed supplementary infant formula and 432 controls; and 112 hyperbilirubinemic neonates exclusively breastfed and 493 controls. The five single nucleotide polymorphisms (SNPs) at nucleotides −53, 211, 686, 1091 and 1456 in the UGT1A1 gene were determined and UGT1A1 activity was estimated. Odds ratios (ORs) of variation status in the UGT1A1 gene and enzyme activity for the development of neonatal hyperbilirubinemia were calculated, respectively. Results: For neonates partially fed supplementary infant formula, the adjusted OR (AOR) for the development of hyperbilirubinemia was significantly higher in the neonates carrying the homozygous variation (211AA) in the UGT1A1 gene than for those carrying the wild type (AOR = 6.00, p