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The genus Talaromyces belongs to the phylum Ascomycota of the kingdom Fungi. Studies have shown that Talaromyces species yield many kinds of secondary metabolites, including esters, terpenes, steroids, alkaloids, polyketides, and anthraquinones, some of which have biological activities such as anti-inflammatory, bacteriostatic, and antitumor activities. The chemical constituents of fungi belonging to the genus Talaromyces that have been studied by researchers over the past several years, as well as their biological activities, are reviewed here to provide a reference for the development of high-value natural products and innovative uses of these resources., 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 © 2022 Lei, Gong, Jin, Wang, Liu, Gao, Liu, Huang, Wang, Wang and Deng.)

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and painful condition in patients who have received chemotherapy. The role of neuromodulation therapy in treating pain and improving neurological function in CIPN remains unclear and warrants evidence appraisal. In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review to assess change in pain intensity and neurological function after implementation of any neuromodulation intervention for CIPN. Neuromodulation interventions consisted of dorsal column spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), or peripheral nerve stimulation (PNS). In total, 15 studies utilized SCS (16 participants), 7 studies utilized DRG-S (7 participants), and 1 study utilized PNS (50 participants). Per the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria, there was very low-quality GRADE evidence supporting that dorsal column SCS, DRG-S, and PNS are associated with a reduction in pain severity from CIPN. Results on changes in neurological function remained equivocal due to mixed study findings on thermal sensory thresholds and touch sensation or discrimination. Future prospective, well-powered, and comparative studies assessing neuromodulation for CIPN are warranted.

Objective: To investigate the therapeutic effect of magnetic resonance and magnetoelectric therapy (MRMT) combined with oral Danhong Tongjing Prescription (DTP) on chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) and the changes in the levels of cytokine-secretory IgA (sIgA), vascular cell adhesion molecule-1 (VCAM-1) and interleukin-8 (IL-8) after treatment., Methods: Totally 200 patients with CP/CPPS of the qi stagnation and blood stasis type were randomly divided into three groups to receive MRMT + DTP (n = 68), MRMT (n = 67) and DTP (n = 65), respectively, all for 12 weeks. After treatment, we compared the total effectiveness rate, patients' scores on NIH-CPSI and traditional Chinese medicine (TCM) syndrome, and the expressions of sIgA, VCAM-1 and IL-8 in the EPS among the three groups of the patients., Results: After treatment, the patients in the MRMT + DTP group, compared with those in the MRMT and DTP groups, showed a significantly higher total effectiveness rate (86.76% vs 79.10% and 78.46%, P < 0.05 and P < 0.01) and lower scores on pain or discomfort (4.61 ± 2.37 vs 5.86 ± 3.26 and 6.94 ± 2.25 P < 0.01), abnormal urination symptoms (2.98 ± 1.75 vs 3.85 ± 2.01 and 3.94 ± 1.95) and quality of life (3.26 ± 1.87 vs 4.54 ± 2.13 and 4.69 ± 1.72). There were statistically significant differences in the total NIH-CPSI scores among the three groups (10.64 ± 5.91 vs 4.59 ± 6.87 vs 15.54 ± 5.76, P < 0.05). The MRMT + DTP group also exhibited a remarkably lower TCM syndrome score than the MRMT and DTP groups (5.56 ± 3.42 vs 7.37 ± 4.57 and 8.16 ± 3.65, P < 0.05). Compared with the baseline, the expressions sIgA, VCAM-1 and IL8 were all markedly decreased after treatment in the MRMT + DTP (Z = －7.170, Z = －7.182, Z = －7.18), MRMT (Z = －6.802, Z = －6.973, Z = －6.768) and DTP groups (Z = －5.963, Z = －6.990 Z = －5.618) (P < 0.05), even more significantly in the former than in the latter two groups (P < 0.05)., Conclusion: Magnetic resonance and magnetoelectric therapy combined with Danhong Tongjing Prescription has a good therapeutic effect on CP/CPPS of the qi stagnation and blood stasis type, probably by regulating sIgA, VCAM-1, IL-8 and other cytokines, activating the function of the immune system, inhibiting inflammation, and promoting the absorption of local inflammatory substances.

Long-term non-healing diabetic wounds are always a serious challenge and a global healthcare burden that needs to be resolved urgently in the clinic. Prolonged inflammation and impaired angiogenesis are the main direct causes of diabetic wounds. With the development of polymer biomaterials, various wound dressings have been created, but a few of them have been applied to the clinical management of diabetic wounds. Here, we developed a mussel-inspired bioactive scaffold consisting mainly of collagen and hyaluronic acid, which are natural biopolymer materials contained in human tissues. First, we fabricated different polydopamine modified lyophilized collagen hyaluronic acid scaffolds under different concentrations of dopamine alkaline solutions, 0.5, 1, 2 ​mg/mL, so named CHS-PDA-0.5, CHS-PDA-1, CHS-PDA-2. After testing their physical and chemical properties, antioxidant effect, inflammation regulation, as well as drug loading and release capabilities, we obtained a bioactive endothelial growth factor (EGF)-loaded wound dressing, CHS-PDA-2@EGF, which can resist reactive oxygen species (ROS) and promote the regeneration of chronic wounds in diabetic rats by reducing inflammation. In addition, the scaffold showed excellent swelling ability, a certain coagulation effect and reasonable degradation. Therefore, the scaffold has great potential to be used in clinical diabetic wound treatment as a low-cost and easily available wound dressing to accelerate chronic wound healing., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wei-Qiang Tan reports administrative support was provided by 10.13039/501100001809National Natural Science Foundation of China. Yong-Zhong Du is a part-time professor of our department from School of Pharmacy, Zhejiang University., (© 2022 The Authors.)

Molecular recognition and self-assembly are often mediated by intermolecular forces involving aromatic π-systems. Despite the ubiquity of such interactions in biological systems and in the design of functional materials, the elusive nature of aromatic π interaction results in that they have been seldom used as a design element for promoting challenging chemical reactions. Described here is a well-engineered catalytic system into which non-covalent π interactions are directly incorporated. Enabled by a lone pair-π interaction and a π-π stacking interaction operating collectively, efficient chiral recognition is successfully achieved in the long-pursued dihydroxylation-based kinetic resolution. Density functional theory calculations shed light on the crucial role played by the lone pair-π interaction between the carbonyl oxygen of the cinchona alkaloid ligand and the electron-deficient phthalazine π moiety of the substrate in the stereoselectivity-determining transition states. This discovery serves as a proof-of-principle example showing how the weak non-covalent π interactions, if ingeniously designed, could be a powerful guide in attaining highly enantioselective catalysis., (© 2022. The Author(s).)

Objective: To compared the traditional Chinese medicine Danhong Tongjing Prescription (DTP) and microsurgery in the treatment of varicocele (VC)-induced infertility and investigate the factors influencing the recovery of semen parameters of the patients., Methods: We retrospectively analyzed the clinical data on 218 cases of VC-induced infertility with qi-deficiency and blood-stasis treated with DTP (n = 86) or by microsurgery (n = 132) in our hospital from January 2017 to July 2019, and compared the semen parameters between the two groups of patients after treatment. With age, course of disease, degree of VC, change of the testis volume, estrogen/testosterone (E/T) ratio and levels of FSH and LH as independent variables, and increased semen parameters after treatment as dependent variables, we constructed a multivariate linear regression model and identified statistically significant independent variables., Results: After treatment, sperm concentration and the percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS) were obviously improved in both the DTP and microsurgery groups, with statistically significant difference between the two groups in sperm concentration and MNS, but not in PMS. Linear regression analysis showed that the severity of VC was an influencing factor for the recovery of sperm concentration after treatment in the DTP group (r = －11.599, Ra2 = 0.044 9) and the course of VC infertility was a factor affecting the recovery of sperm count in the microsurgery group (r = －1.837, Ra2 = 0.035 7)., Conclusion: DTP is comparable to microsurgery in improving sperm motility while microsurgery is more effective in increasing the percentage of MNS in the treatment of VC-induced infertility. Early surgery is recommended for the treatment of infertility induced by severe bilateral VC, and DTP can be selected for infertility caused by mild or moderate bilateral VC if the patient is unwilling to accept surgery or microsurgery is inaccessible in the hospital.

Malignant mesothelioma (MM) is a long latency, poor prognosis and asbestos exposure related malignant disease. Long non-coding RNA (lncRNA) is a kind of RNA with a length of more than 200 nucleotides that does not encode protein. It plays an important role in epigenetic regulation, cell cycle regulation and cell differentiation regulation. Recent studies have shown that the abnormal expression or function of lncRNA is closely related to the diagnosis and prognosis of MM. In this paper, the lncRNA research on MM is reviewed to better understand the role of lncRNA in MM.

The mechanistic uniqueness and versatility of borrowing hydrogen catalysis provides an opportunity to investigate the controllability of a cascade reaction, and more importantly, to realize either one or both of chiral recognition and chiral induction simultaneously. Here we report that, in a borrowing hydrogen cascade starting from racemic allylic alcohols, one of the enantiomers could be kinetically resolved, while the other enantiomer could be purposely converted to various targeted products, including α,β-unsaturated ketones, β-functionalized ketones and γ-functionalized alcohols. By employing a robust Ru-catalyst, both kinetic resolution and asymmetric induction were achieved with remarkable levels of efficiency and enantioselectivity. Density functional theory (DFT) calculations suggest that corresponding catalyst-substrate π-π interactions are pivotal to realize the observed stereochemical diversity., (© 2021 Wiley-VCH GmbH.)

No matter through asymmetric reduction of ketones or kinetic resolution of secondary alcohols, enantioselective synthesis of the corresponding secondary alcohols is challenging when the two groups attached to the prochiral or chiral centers are spatially or electronically similar. For examples, dialkyl (sp 3 vs. sp 3 ), diaryl (sp 2 vs. sp 2 ), and aryl-alkenyl (sp 2 vs. sp 2 ) alcohols are difficult to produce with high enantioselectivities. By exploiting our recently developed Ru-catalysts of minimal stereogenicity, we reported herein a highly efficient kinetic resolution of aryl-alkenyl alcohols through hydrogen transfer. This method enabled such versatile chiral building blocks for organic synthesis as allylic alcohols, to be readily accessed with excellent enantiomeric excesses at practically useful conversions.

As part of our search for compounds with cytotoxicity from endophytes of traditional Chinese medicines, two novel nor-sesquiterpenoids ( 1 - 2 ) with a new skeleton containing a tetrahydrofuran moiety were isolated form a rice medium of Fusarium tricinctum , an endophytic fungus isolated from the root of Ligusticum chuanxiong . The structures of these two previously undescribed compounds were elucidated by interpretation of the spectroscopic evidences including NMR correlations as well as MS data. The absolute configurations of these two compounds were confirmed by TD-DFT-ECD calculations. An MTT assay indicated that compound 1 exhibited moderate cytotoxic activity against MV4-11 with an IC 50 value of 22.29 μM.

Inflammatory bowel disease (IBD) is a disease characterized by intestinal inflammation with immune dysregulation and intestinal microecological imbalance. In a dextran sulfate sodium salt (DSS)-induced IBD mouse model, noni ( Morinda citrifolia L.) fruit polysaccharides (NFP) with homogalacturonan and rhamnogalacturonan-I domain decreased the concentration of serum LPS, TNF-α, and IL-17 by 84, 42, and 65%, respectively. It was abolished when intestinal microbiota were depleted by antibiotics. Sequencing analysis of gut microbiota showed an attenuated disruption of the microbial composition in the DSS+NFP group. Targeted metabolomic analysis revealed that NFP upregulated the content of acetic acid, propionic acid, and butyric acid by onefold but reduced isobutyric acid and isovaleric acid contents. NFP also inhibited JNK, ERK, and NF-κB phosphorylation of IBD mice. Taken together, the mechanism of NFP alleviating IBD is related to the intestinal microecological balance to inhibit inflammatory signaling pathways. This study provides a basis for NFP as a cheap intervention for the prevention and treatment of IBD patients.

The global health emergency generated by coronavirus disease-2019 has prompted the search for immunomodulatory agents. There are many potential natural products for drug discovery and development to tackle this disease. One of these candidates is the Ganoderma lucidum fungal immunomodulatory protein (FIP-glu). In the present study, we clarify the influences of N-linked glycans on the improvement of anti-inflammatory activity and the potential mechanisms of action. Four proteins, including FIP-glu (WT) and its mutants N31S, T36N and N31S/T36N, were successfully expressed in P. pastoris, of which T36N and N31S/T36N were glycoproteins. After treatment with peptide-N-glycosidase F, the results of SDS-PAGE and Western blot showed that the glycan moiety was removed completely, indicating that the glycan moiety was N-linked. This was also demonstrated by UPLC-qTOF-MS. The cytotoxicity assay showed that N-linked glycans decreased the cytotoxicity of WT; while, the RT-qPCR assay showed that N-glycosylated WT regulated the mRNA expression of IL-6 and TGF-β1. The Western blot results showed that N-glycosylated WT reduced the phosphorylation level of p38 MAPK. In conclusion, our findings revealed a novel mechanism by which N-glycosylation of FIP-glu improved its anti-inflammatory activity through the regulation of the expression of inflammatory cytokines in RAW264.7 via inhibition of p38 MAPK phosphorylation. It was proved that N-glycosylation significantly improved the functional properties of FIP-glu, providing theoretical and technical support for expanding the application of FIPs in the food and pharmaceutical industries.

The gold-spotted pond frog ( Pelophylax chosenicus ) is an endangered amphibian species in South Korea. In order to obtain ecological information regarding the gold-spotted pond frog's habitat environment and biological interactions, we applied stable isotope analysis to quantify the ecological niche space (ENS) of frogs including black-spotted pond frogs ( P. nigromaculatus ) and bullfrogs ( Lithobates catesbeianus ) within the food web of two different habitats-an ecological wetland park and a rice paddy. The gold-spotted pond frog population exhibited a broader ENS in the ecological wetland park than in the rice paddy. According to the carbon stable isotope ratios, gold-spotted pond frogs mainly fed on insects, regardless of habitat type. However, the results comparing the range of both carbon and nitrogen stable isotopes showed that gold-spotted pond frogs living in the rice paddy showed limited feeding behavior, while those living in the ecological wetland park fed on various food sources located in more varied trophic positions. Although the ENS of the gold-spotted pond frog was generally less likely to be overlapped by that of other frog species, it was predicted to overlap with a high probability of 87.3% in the ecological wetland park. Nevertheless, gold-spotted pond frogs in the ecological wetland park were not significantly affected by the prey competition with competitive species by feeding on other prey for which other species' preference was low. Since these results show that a habitats' food diversity has an effect on securing the ENS of gold-spotted pond frogs and prey competition, we recommend that the establishment of a food environment that considers the feeding behavior of gold-spotted pond frogs is important for the sustainable preservation of gold-spotted pond frogs and their settlement in alternative habitats.

Background: It is well known that morning blood pressure surge increases the risk of myocardial events in the first several hours post-awakening. This meta-analysis was performed to compare the antihypertensive efficacy of morning and bedtime dosing on decreasing morning blood pressure surge., Methods: Articles in 4 databases about clinical trials of ingestion time of antihypertensive drugs were searched and performed a meta-analysis to evaluate the different effects on morning blood pressure and absolute blood pressure (BP) reduction from baseline of between bedtime administration (experimental group) and morning awaking administration (control group)., Results: The aim of this study is to compare the antihypertensive efficacy of morning and bedtime dosing on decreasing morning blood pressure surge., Conclusions: The bedtime will provide evidence support for clinicians and patients for reducing morning blood pressure surge., Ethics and Dissemination: This study does not require ethical approval., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Mesangial cells played a central role in the pathophysiology of diabetic nephropathy (DN). Our goal was to evaluate the molecular mechanism that regulates loss of BMP7 protein expression in DN. The mRNA and protein levels of BMP7 or UBE4A were detected using qRT-PCR and Western blot respectively. Mass spectrometry and co-immunoprecipitation were used to explore the E3 ligase which regulated BMP7 post-translationally. We initially confirmed that BMP7 protein, but not mRNA, is downregulated when cultured under high glucose mimicking DN conditions, which was rescued by MG-132 treatment. Proteomic analysis of NRK-52E cells ± MG-132 revealed a list of ubiquitin ligases associated with BMP7. Knockdown of the ubiquitin ligase UBE4A stabilized BMP7 expression in NRK-52E cells grown under high glucose conditions. Concurrent overexpression experiments confirmed that UBE4A is the ubiquitin ligase that degrades BMP7. Co-immunoprecipitation analysis confirmed that BMP7 and UBE4A interact. BMP7 expression in DN is regulated by post-translational mechanism.

The borrowing-hydrogen (or hydrogen autotransfer) process, where the catalyst dehydrogenates a substrate and formally transfers the H atom to an unsaturated intermediate, is an atom-efficient and environmentally benign transformation. Described here is an example of an asymmetric borrowing-hydrogen cascade for the formal anti-Markovnikov hydroamination of allyl alcohols to synthesize optically enriched γ-secondary amino alcohols. By exploiting the Ru-( S )- i PrPyme catalyst with minimal stereogenicity, a cascade process including dehydrogenation, conjugate addition, and asymmetric reduction was developed. The mild conditions, functional group tolerance, and broad substrate scope (54 examples) demonstrate the synthetic practicality of the catalytic system.

A multicomponent catalytic reaction between ketones, Morita-Baylis-Hillman (MBH) carbonates and trifluoromethylthiolating agents is devised for straightforwardly accessing two products, α-trifluoromethylthiolated ketones and α-methylene β-amino esters in a one pot fashion. Particularly noteworthy is that the trifluoromethylthiolating reagent is employed as both the nitrogen and SCF3 source initiated by DABCO. This mild one pot strategy enjoys atom- and step-economic attractiveness, for direct introduction of an SCF3 group onto a variety of acyclic ketones, which have been considered as less effective and less developed substrates.

Despite the significant research that has been carried out to improve cycling performance of lithium ion batteries (LIB) with silicon (Si) based composite electrodes, limited studies have been performed on these materials to evaluate the effects of internal microstructural changes and stress evolution on the electrochemical performance. Here, combined ex situ and in situ investigations on the accommodation of volume expansion in Si-based nanocomposite electrodes are reported. This work emphasizes the importance of conductive agents in light of the poor electronic conductivity of Si. A detailed comparison between commonly used carbon black (CB) and reduced graphene oxide (rGO) shows that these materials have substantial effects on microstructural evolution and internal stress in Si based composite electrodes that are employed in lithium ion cells. This study provides the first monitoring of stress evolution in Si-rGO based composite electrode during electrochemical cycling using in situ wafer curvature measurements. The prepared Si-rGO based electrode exhibits almost 10 times lower stress generation and consequently higher cycling performance in electrochemical cells. The resulting 3D networked structure not only acts as an electronic conduit to the encapsulated active materials but also serves as a mini-electrochemical reaction chamber which hinders the formation of the solid electrolyte interphase (SEI) and limits the pulverization of active material and the evolution of severe stress during cycling. Moreover, investigations of the microstructural changes and internal charge transfer resistance in the electrodes after cycling provide further evidence that rGO produces superior structures for energy storage.

Ganoderma lucidum is a widely used medicinal mushroom in traditional Chinese medicine that creates a diverse set of bioactive compounds. Highland barley, a typical nutrition-balanced crop, is not convenient for direct consumption but its nutritional characteristics meet the modern requirements of health food. In the present study, barley grains were used as substrates on solid-state fermentation (SSF) of G. lucidum. Statistical optimization of media composition was employed for enhancing the production of polysaccharides. Peptone, medlar, and KH2PO4 were identified as the most important components for producing polysaccharide. Based on the one-factor-at-a-time experimentation, a quadratic regression model with the polysaccharide contents as the response value was established by central composite design (CCD). The results showed that the predicted variables were 2.38% peptone, 1.14% medlar, and 0.25% KH2PO4 for the maximum yield of predicted polysaccharides of 11.64% in the fermented substrate. The experimental polysaccharides obtained using the predicted optimum media composition constituted 11.61% of the fermented substrate, which validates the high degree of accuracy of optimization for enhanced production of polysaccharides by SSF. This study suggested that in the process of barley grains fermentation by G. lucidum for polysaccharides production, the optimized SSF substrate consists of 71.4% barley grains, 2.38% peptone, 1.14% medlar, 0.25% KH2PO4, 2.5% glucose, 0.25% MgSO4 · 7H2O, and 1% CaCO3. According to this study, the strain G. lucidum 00679 showed a good fermentation property by optimizing the media. It might be a candidate industrial strain for further process optimization and scale-up study.

Two new terpene glycosides ( 1 - 2 ) along with two known analogs ( 3 - 4 ) were obtained from the root of Sanguisorba officinalis, which is a common traditional Chinese medicine (TCM). Their structures were elucidated by nuclear magnetic resonance (NMR), electrospray ionization high resolution mass spectrometry (HRESIMS), and a hydrolysis reaction, as well as comparison of these data with the literature data. 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). An anti-inflammatory assay based on the zebrafish experimental platform indicated that compound 1 had good anti-inflammatory activity in vivo by not only regulating the distribution, but also by reducing the amount of the macrophages of the zebrafish exposed to copper sulfate.

Mutations within the Shank3 gene, which encodes a key postsynaptic density (PSD) protein at glutamatergic synapses, contribute to the genetic etiology of defined autism spectrum disorders (ASDs), including Phelan-McDermid syndrome (PMS) and intellectual disabilities (ID). Although there are a series of genetic mouse models to study Shank3 gene in ASDs, there are few rat models with species-specific advantages. In this study, we established and characterized a novel rat model with a deletion spanning exons 11-21 of Shank3 , leading to a complete loss of the major SHANK3 isoforms. Synaptic function and plasticity of Shank3 -deficient rats were impaired detected by biochemical and electrophysiological analyses. Shank3 -depleted rats showed impaired social memory but not impaired social interaction behaviors. In addition, impaired learning and memory, increased anxiety-like behavior, increased mechanical pain threshold and decreased thermal sensation were observed in Shank3 -deficient rats. It is worth to note that Shank3 -deficient rats had nearly normal levels of the endogenous social neurohormones oxytocin (OXT) and arginine-vasopressin (AVP). This new rat model will help to further investigate the etiology and assess potential therapeutic target and strategy for Shank3 -related neurodevelopmental disorders.

β-Glucosidase activity assays constitute an important indicator for the early diagnosis of neonatal necrotizing enterocolitis and qualitative changes in medicinal plants. The drawbacks of the existing methods are high consumption of both time and reagents, complexity in operation, and requirement of expensive instruments and highly trained personnel. The present study provides a simplified, highly selective, and miniaturized glucometer-based strategy for the detection of β-glucosidase activity. Single-factor experiments showed that optimum β-glucosidase activity was exhibited at 50 °C and pH 5.0 in a citric acid-sodium citrate buffer when reacting with 0.03 g/mL salicin for 30 min. The procedure for detection was simplified without the need of a chromogenic reaction. Validation of the analytical method demonstrated that the accuracy, precision, repeatability, stability, and durability were good. The linear ranges of β-glucosidase in a buffer solution and rat serum were 0.0873-1.5498 U/mL and 0.4076-2.9019 U/mL, respectively. The proposed method was free from interference from β-dextranase, snailase, β-galactosidase, hemicellulase, and glucuronic acid released by baicalin. This demonstrated that the proposed assay had a higher selectivity than the conventional dinitrosalicylic acid (DNS) assay because of the specificity for salicin and unique recognition of glucose by a personal glucose meter. Miniaturization of the method resulted in a microassay for β-glucosidase activity. The easy-to-operate method was successfully used to detect a series of β-glucosidases extracted from bitter almonds and cultured by Aspergillus niger. In addition, the simplified and miniaturized glucometer-based assay has potential application in the point-of-care testing of β-glucosidase in many fields, including medical diagnostics, food safety, and environmental monitoring.

Saemangeum Reservoir in South Korea is an estuarine system enclosed by a dyke construction, where seawater inflow and retained water outflow are managed by the opening/closing of sluice gates installed in the southern part of the dyke. An exchange of the reservoir water can cause spatiotemporal fluctuations in the salinity and trophic state, which are major drivers determining variation in the composition of biological communities in estuarine systems. Here, we investigated the seasonal and spatial variability in the copepod community and environmental conditions (water temperature, salinity, transparency, chlorophyll a concentration, total nitrogen, total phosphorus and Carlson's trophic state index) based on seasonally conducted field monitoring in the Saemangeum Reservoir from July 2013 to January 2018. In addition to the role of temperature, salinity and chlorophyll a concentration in structuring the copepod community and diversity, the biological indices of copepods with respect to salinity range and trophic state, were evaluated. The spatiotemporal variability in the salinity and trophic state variables showed contrasting patterns, and chlorophyll a concentration was negatively affected by salinity, indicating that the reservoir water was being highly exchanged with opening of the sluice gates. The mean trophic state index values, however, were constant in the eutrophic state (50-70). Dominant copepods were Acartia (A. hudsonica, A. sinjiensis, Acartia spp.) and Oithona (O. davisae and Oithona spp.), which are common species in eutrophic neritic water. Variation in the copepod community was mainly associated with the seasonal succession of the dominant species rather than a spatial gradient (from around the estuary to the sluice gates); however, site-specific differences in frequencies of several non-dominant species could be detected around the estuary (Sinocalanus tenellus) and the sluice gates (Centropages spp., Tigriopus spp. and Labidocera rotunda). The copepod diversity increased with species-richness from around the estuary to the sluice gates, which could result from variation in the site-specific location of non-dominant species. The frequency of particular species was also able to discriminate in terms of the salinity range (oligohaline: A. pacifica, S. tenellus and A. sinjiensis; mesohaline: Pseudodiaptomus inopinus; and polyhaline: C. abdominalis and Centropages spp.) and the trophic state (mesotrophic: C. abdominalis, Calanus sinicus and Centropages spp.; and hypereutrophic: S. tenellus, P. inopinus and Sinocalanus spp.). The findings from this study not only identify the factors determining spatiotemporal variation in the copepod community in the Saemangeum Reservoir, but also expand the applicability of copepods as biological indicators of conditions associated with salinity range and trophic state in other enclosed estuarine systems., Competing Interests: The authors have declared that no competing interests exist.

A common complication of both type I and type II diabetes is nephropathy, characterized by accumulation of extracellular matrix in the glomerular mesangium. This indicates a central role of mesangial cells in the pathophysiology of diabetic nephropathy. Using the proteomic approach, it was earlier elucidated in a rat model that the proteasome subunit-α type-6 protein (PSMA6) is suppressed in the renal cortex in nephropathic kidney. However, the underlying mechanism effecting suppression of PSMA6 protein in the renal cortex is not yet known. Twenty diabetic patients were enrolled and the expression level of PSMA6 in them was detected by immunohistochemistry. The protein and mRNA expression levels of PSMA6 in NRK-52E cells under high glucose condition were determined by Western blot and quantitative real-time PCR, respectively. Dual luciferase assay was used to detect the relationship of PSMA6 and miR-4490. Our results show that PSMA6 protein is down-regulated in patients with diabetic nephropathy compared with healthy control. Using the NRK-52E cell line cultured under high glucose condition as an in vitro model of diabetic nephropathy, we show that loss of PSMA6 protein expression occured independent of changes the in PSMA6 mRNA expression. We next elucidate that PSMA6 mRNA is post-transcriptionally regulated by the microRNA (miRNA)-4490, whose expression is inversely correlated to PSMA6 protein expression. Using reporter assays we show that PSMA6 is a direct target of the miR-4490. Exogenous manipulation of miR-4490 levels modulated expression of PSMA6, indicating that miR-4490 can be tested as a biomarker for nephropathy in diabetic patients., (© 2018 The Author(s).)

Aim: This study aims to investigate the effect of human umbilical cord mesenchymal stem cell exosomes (hucMSC-Ex) on placental tissue and angiogenesis in rats with preeclampsia (PE)., Method: The expression of MSC surface markers were identified by flow cytometry. Alizarin red staining and oil red O staining were used to examine osteogenic and adipogenic differentiation of hucMSCs. Western blotting was used to determine expressions of CD63 and CD81 in hucMSC-Ex. PE rat models were established using endothelial nitric oxide synthase, eNOS)N G -Nitro-l-arginine Methyl Ester, which were then treated with exosome (Exo) of low dosage (L-Exo), Exo of medium dosage (M-Exo) and Exo of high dosage (H-Exo). The blood pressure at the 15d, 17d and 19d of pregnancy and 24-h urinary protein were measured. TUNEL staining and immunohistochemistry were applied to detect the cell apoptosis and micro-vascular density (MVD) in placental tissues, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to examine serum levels of vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase receptor-1 (sFlt1)., Results: In vitro cultured hucMSCs showed expression of MSC surface markers (CD29, CD90 and CD105), and no expression of CD34 and CD45. Besides, the isolated exosomes expressed the exosome markers (CD63 and CD81). In response to the treatment of L-Exo, M-Exo and H-Exo, the blood pressure of PE rat models on the 17 d and the 19 d as well as the 24-h urinary protein were substantially decreased. Moreover, at the 21 d, PE rat models treated with L-Exo, M-Exo and H-Exo exhibited an increase in the number and quality of fetuses, placenta quality, MVD and VEGF expression, but substantial decreased cell apoptosis and expression of sFlt1. The influence of Exos was exerted in a dosage dependent manner., Conclusion: hucMSC-Ex, in a dose-dependent manner, can improve the morphology of placental tissue in rats with PE, by inhibiting cell apoptosis and promoting angiogenesis in placental tissue., (Copyright © 2018. Published by Elsevier Masson SAS.)

Objective: To explore the efficacy and safety of chimeric antigen receptor T (CAR-T) cells in the treatment of central nervous system leukemia (CNSL). Methods: Two leukemia patients with CNSL were treated with CD19-CAR-T cells. The process and results of the entire treatment is reported and related literature review is conducted. Results: The patients were diagnosed as acute myeloid leukemia (AML)-M(2) with B lymphoid antigen expression and B cell acute lymphoblastic leukemia(B-ALL) by morphology and immunophenotype assay. The immunophenotype was consistent with the abnormal manifestations of AML-M(2) and B-ALL. Their clinical manifestations and laboratory tests met the diagnostic criteria of CNSL. The diagnosis was clear and the two patients were treated with CD19-CAR-T cell immunotherapy. Central nervous system symptoms were relieved. The imaging abnormalities of patient one has disappeared but cytokines release syndrome (CRS) occurred during the treatment. Cerebrospinal fluid of patient two was negative and no obvious CRS reaction was found. Conclusions: CAR-T cell immunotherapy is likely to induce the remission of CNSL and improve the prognosis.

Five new polyketides, including two pairs of enantiomers and a racemate, were isolated from the fermentation broth of Aspergillus fumigatus , an endophytic fungus isolated from Cordyceps sinensis . Their structures were identified using one-dimensional (1D) and two-dimensional (2D) NMR experiments, and the absolute configurations of the enantiomers were confirmed using electronic circular dichroism (ECD) calculations. Compounds 1a and 2a exhibited inhibitory activity against the MV4-11 cell line in vitro, with IC 50 values of 23.95 µM and 32.70 µM, respectively.

Although recent progress has been made in introducing an SCF3 functionality into a variety of molecules, enantioselective trifluoromethylthiolation remains challenging, especially the α-trifluoromethylthiolation of carbonyl compounds. The present study describes a diastereo and enantioselective Cu-catalyzed tandem 1,4-addition/trifluoromethylthiolation of acyclic enones. The tandem reaction enables the asymmetric integration of the -SCF3 group to carbonyl compounds, establishing chiral tertiary α-carbon centers and affording α-SCF3-β-substituted carbonyl compounds in 50-92% yields with up to 20 : 1 dr and 96% ee.

Treatment of intervertebral disc degeneration (IDD) seeks to prevent senescence and death of nucleus pulposus (NP) cells. Previous studies have shown that sirt6 exerts potent anti-senescent and anti-apoptotic effects in models of age-related degenerative disease. However, it is not known whether sirt6 protects against IDD. Here, we explored whether sirt6 influenced IDD. The sirt6 level was reduced in senescent human NP cells. Sirt6 overexpression protected against apoptosis and both replicative and stress-induced premature senescence. Sirt6 also activated NP cell autophagy both in vivo and in vitro. 3-methyladenine (3-MA) and chloroquine (CQ)-mediated inhibition of autophagy partially reversed the anti-senescent and anti-apoptotic effects of sirt6, which regulated the expression of degeneration-associated proteins. In vivo, sirt6 overexpression attenuated IDD. Together, the data showed that sirt6 attenuated cell senescence, and reduced apoptosis, by triggering autophagy that ultimately ameliorated IDD. Thus, sirt6 may be a novel therapeutic target for IDD treatment.

The significant positive correlation between ghrelin and iron and hepcidin levels in the plasma of children with iron deficiency anemia prompted us to hypothesize that ghrelin may affect iron metabolism. Here, we investigated the effects of fasting or ghrelin on the expression of hepcidin, ferroportin 1 (Fpn1), transferrin receptor 1 (TfR1), ferritin light chain (Ft-L) proteins, and ghrelin, and also hormone secretagogue receptor 1 alpha (GHSR1α) and ghrelin O-acyltransferase (GOAT) mRNAs in the spleen and/or macrophage. We demonstrated that fasting induces a significant increase in the expression of ghrelin, GHSR1α, GOAT, and hepcidin mRNAs, as well as Ft-L and Fpn1 but not TfR1 proteins in the spleens of mice in vivo. Similar to the effects of fasting on the spleen, ghrelin induced a significant increase in the expression of Ft-L and Fpn1 but not TfR1 proteins in macrophages in vitro. In addition, ghrelin was found to induce a significant enhancement in phosphorylation of ERK as well as translocation of pERK from the cytosol to nuclei. Furthermore, the increased pERK and Fpn1 induced by ghrelin was demonstrated to be preventable by pre-treatment with either GHSR1α antagonist or pERK inhibitor. Our findings support the hypothesis that fasting upregulates Fpn1 expression, probably via a ghrelin/GHSR/MAPK signaling pathway., (© 2017 Wiley Periodicals, Inc.)

To understand the potential mechanisms involved in the beneficial effects of aspirin (ASA) in mood disorders, Alzheimer's (AD) and Parkinson's disease (PD), we investigated the effects of ASA on the expression of iron transport proteins transferrin receptor 1 (TfR1), ferroportin 1 (Fpn1), and iron storage protein ferritin light chain (Ft-L) in interleukin-6 (IL-6)-treated PC-12 cells. We demonstrated that IL-6 alone could induce a severe decline in Fpn1 expression and cell viability, and an increase in Ft-L protein, while ASA could markedly diminish the effects of IL-6 on these parameters. We also found that IL-6 significantly increased hepcidin expression and janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) phosphorylation, while ASA also observably suppressed these IL-6-induced effects. The data imply that ASA increases Fpn1 expression by inhibiting hepcidin expression via the IL-6/JAK/STAT3 pathway and show that the reduced content of Ft-L is due to the increased Fpn1 and subsequent iron release in the cells. The reduction of iron in neuronal cells by the increased expression of Fpn1 might be partly associated with the beneficial effects of ASA on mood disorders, AD and PD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Treatments for osteoarthritis (OA) seek to restore chondrocyte function and inhibit cell apoptosis. Panax quinquefolium saponin (PQS) is the major active ingredient of Radix panacis quinquefolii (American ginseng), and has been demonstrated to exert anti-inflammatory and anti-apoptotic effects in various diseases. However, any potential effect of PQS on the pathological process of OA remains unclear. This work aimed to explore the role of PQS in chondrocytes and to clarify its potential mechanisms. We showed that PQS treatment could protect chondrocytes against endoplasmic reticulum (ER) stress and associated apoptosis induced by interleukin (IL)-1β. Also, PQS further attenuated triglyceride (TG)-induced ER stress and associated apoptosis. Moreover, PQS may inhibit the ER stress-activated NF-κB pathway and associated inflammatory response in chondrocytes. Finally, PQS abolished rat cartilage degeneration in an in-vivo OA model of the knee joint. Our results indicate that PQS may be a potential novel treatment for OA., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The concentration, potential source and health risks of 16 polycyclic aromatic hydrocarbons (PAHs) in the atmosphere of Dajiuhu, Shennongjia, China, were studied. Polyurethane foam (PUF) Passive air samplers (PAS) were settled. The results indicated that the total concentrations of 16 PAHs in different samples ranged from 6.94 to 184.23 ng·m -3 , with the mean of 30.36 ng·m -3 . The dominant compounds were low rings PAHs, such as Phe, Nap, Pyr, Fla, Flu and Ant. Compared with other regions, the PAHs pollution of Dajiuhu atmosphere was at a low level. Higher PAHs concentrations were detected in nearby Deer farm, Dajiuhu peat area and Dajiuhu Wetland Authority. Higher PAHs concentrations were detected in autumn and winter, whereas lower concentrations were detected in spring and summer. Potential pollution sources of PAHs were investigated by diagnostic ratios and backward trajectory analysis, which indicated that coal and biofuel combustion, vehicle emissions and petroleum were the main sources. PAHs of Dajiuhu in air not only came from local emission, but also originated from Hubei, Henan and Hunan's atmosphere transport for most part and long range transport from northwest direction for small part. Health risks assessment results showed that the annual average concentration of total Benzo(a)pyrene-equivalent carcinogenic potency (∑BaP eq ) was 0.208 ng·m -3 , lower than the value recommended by Ambient Air Quality Standard of China(GB 3095-2012, 1 ng·m -3 ), indicating a low carcinogenic risk for the local residents.

Synthetic biology has been applied to direct improvement of valuable metabolite productions. Tacrolimus (FK506), a clinically used immunosuppressive agent isolated from many Streptomyces, is produced by fermentation in industry. Here we chose FK506 as an example to review recent progress in improving FK506 production, including enhancing transcription levels of biosynthetic genes, accelerating post-translational modification levels of biosynthetic enzymes, increasing activities of rate limiting enzymes, and rational supplement of limited precursors. FK506 production was increased from 25 % to sevenfold by these synthetic biology approaches.

A highly efficient asymmetric synthesis of chiral thioflavanones is developed via conjugate addition of arylzinc reagents to thiochromones using Rh(COD)Cl 2 /(R)-3,4,5-MeO-MeOBIPHEP catalyst. This method overcomes catalyst poisoning and substrate inertness and affords a series of chiral thioflavanones (2-arylthiochroman-4-ones) in good yields (up to 91% yield) with excellent ee values (up to 97% ee). The established asymmetric synthesis paves the way for further pharmaceutical studies.

Bismuth triflate (Bi(OTf)3) is identified as an efficient catalyst for the direct addition of isocyanides to 2H-chromene acetals. The large scope of isocyanides and chromene acetals makes them suitable substrates in this catalytic system. By this synthetic strategy, a polyfunctional molecular scaffold, 2-carboxamide-2H-chromenes could be prepared efficiently in one step up to 95% yield. In addition, this efficient and practical protocol proceeded smoothly in the gram scale even when the catalytic loading was reduced to 2 mol%.

Many polyketides show biological activities and have thus been applied in clinics, as food additives, and in agriculture. Type II thioesterases (TEIIs) play an important role in polyketide biosynthesis. Most TEIIs belong to α/β-hydrolase family and usually contain a catalytic triad Ser-His-Asp. In polyketide biosynthesis, TEIIs can play an editing role by removal of aberrant non-extendable acyl units in elongation steps, a starter unit selection role by removal of unfavored starter acyl units in initiation steps, and a releasing role by removal of final product in termination steps. Complementation of TEIIs has been observed and applied.

This study was designed to use iTRAQ technology coupled with 2D LC-MS/MS to study the comparative proteomics of different processing technology for pilose antler. 1015 proteins were identified with 2D LC combined with MOLDI TOF/TOF mass spectrometry. Comparative analysis with Protein Pilot (Version 4.5) revealed that 87 proteins were changed (P ≤ 0.05, the ratio of > 1.50 or < 0.60 as the threshold selection of difference proteins), of which 24 were up regulated and 33 were down regulated in the traditional frying process (TFP) compared with the fresh pilose antler (P ≤ 0.05). 7 significant different proteins (P ≤ 0.001), most of these significantly changed proteins were found to be involved in calcium ion binding and ATP binding associated with human healthy. Freeze drying with protective agent (FDP) (Trehalose) can improve the content of significantly different proteins (P ≤ 0.001) including Collagen alpha-1 (XII) chain (COL12A1) and Collagen alpha-1 (II) chain (COL2A1). The significant function involves in platelets activating, maintenance of spermatogonium, and disorder expression in tumor cells. The functional annotation by Hierarchical clustering and GO (gene ontology) showed that the main molecule functions of the proteins significantly changed in these processes were involved in binding (52.7%), catalytic (25.3%), structural molecule and transporter (6.6%).

Acyltransferases (ATs) play an essential role in the polyketide biosynthesis through transferring acyl units into acyl carrier proteins (ACPs) via a self-acylation reaction and a transacylation reaction. Here we used AT10FkbA of FK506 biosynthetic polyketide synthase (PKS) from Streptomyces tsukubaensis YN06 as a model to study the specificity of ATs for acyl units. Our results show that AT10FkbA can form both malonyl-O-AT10FkbA and methylmalonyl-O-AT10FkbA in the self-acylation reaction, however, only malonyl-O-AT10FkbA but not methylmalonyl-O-AT10FkbA can transfer the acyl unit into ACPs in the transacylation reaction. Unlike some ATs that are known to control the acyl specificity in self-acylation reactions, AT10FkbA controls the acyl specificity in transacylation reactions.

Yeputaoteng is the dried ground part of Ampelopsis sinica (Miq.) W.T. Wang, which is widely used in traditional Chinese medicine for preventing and treating tumors, chronic nephritis, hepatitis, rubella, traumatic bleeding, stomach heat and vomiting. A simple and reliable method using high-performance liquid chromatography with diode array detection (HPLC-DAD) was developed for the simultaneous determination of dihydromyricetin and resveratrol in Yeputaoteng. The chromatographic analysis was performed on a Dikma C18 column (250 × 4.6 mm, 5 µm) at 30°C with a gradient elution of acetonitrile and 0.1% phosphoric acid at a flow rate of 1 mL/min, and used ultraviolet detection at 292 and 306 nm. The established method was validated in terms of linearity, precision, reproducibility, stability and recovery. The calibration curves showed good linear regression (R(2) > 0.9994). Limits of detection and quantification fell in the ranges of 1.47-2.48 and 2.93-4.97 µg/mL, respectively. The mean recovery of dihydromyricetin and resveratrol was 104.1% [relative standard deviation (RSD): 2.94%] and 100.8% (RSD: 2.80%), respectively. The quantitative results indicated that the HPLC-DAD method can be effectively applied to the quality control of Yeputaoteng and its preparations.

We found that chemoselectivity of the crossed acyloin product is controlled by the adjustment of the aromatic aldehyde/aliphatic aldehyde ratio. Moreover, we observed the persistent catalytic activity of the homogeneous NHC catalyst in a solution due to NHC catalyst robustness.

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. We tested megestrol acetate (MA) against placebo in the treatment of advanced HCC., Methods: From 2002 through 2007, this randomised double-blind trial enrolled 204 patients with treatment-naive advanced HCC (Eastern Cooperative Oncology Group (ECOG) performance rating of 0-3) from specialist care centres in six Asia-Pacific nations. Patients received placebo or MA (320 mg day(-1)). End points were overall survival (OS) and quality of life., Results: An adverse but not statistically significant difference in OS was found for MA vs placebo: median values 1.88 and 2.14 months, respectively (hazard ratio (HR)=1.25, 95% CI=0.92-1.71, P=0.16). However, OS was similar among patients of good functional status (Child-Pugh A and ECOG 0, 1 or 2) (44.3%) in both treatment groups, with the adverse effect of MA confined to those of poor status. Megestrol acetate patients had a worse global health status (not statistically significant) but reduced levels of appetite loss and nausea/vomiting., Conclusion: Megestrol acetate has no role in prolonging OS in advanced treatment-naive HCC. Overall survival with placebo differed markedly from that in similar trials conducted elsewhere, suggesting therapeutic outcomes may be strongly dependent on ECOG status and Child-Pugh score.

This study examined whether ethyl pyruvate (EP) promotes the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. MPTP induced degeneration of nigrostriatal DA neurons and glial activation as visualized by tyrosine hydroxylase, macrophage Ag complex-1, and/or glial fibrillary acidic protein immunoreactivity. Western blotting and immunohistochemistry showed activation of microglial NADPH oxidase and astroglial myeloperoxidase (MPO) and subsequent reactive oxygen species/reactive nitrogen species production and oxidative DNA damage in the MPTP-treated substantia nigra. Treatment with EP prevented degeneration of nigrostriatal DA neurons, increased striatal dopamine levels, and improved motor function. This neuroprotection afforded by EP was associated with the suppression of astroglial MPO expression, NADPH oxidase-, and/or inducible NO synthase-derived reactive oxygen species/reactive nitrogen species production by activated microglia. Interestingly, EP was found to protect DA neurons from 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia but not in neuron-enriched mesencephalic cultures devoid of microglia. The present findings show that EP may inhibit glial-mediated oxidative stress, suggesting that EP may have therapeutic value in the treatment of aspects of Parkinson's disease related to glia-derived oxidative damage.

A facile method for the intermolecular Stetter reaction of various Michael acceptors with acetaldehyde as a biomimetic acylanion source was realized using N-heterocyclic carbene catalysis. This catalytic system has also been applied to the enantioselective Stetter reaction and resulted in moderate to good enantioselectivities for the corresponding Stetter products.

A cobalt-Xantphos-catalyzed, LiCl-mediated system has been developed for the direct and expedient preparation of arylzinc reagents in THF from the corresponding aryl iodides, bromides, and chlorides. Owing to the use of THF as a versatile solvent, the thus-formed arylzinc reagents displayed a high degree of compatibility with a variety of conventional as well as newly emerging metal-catalyzed cross-coupling reactions.

An unprecedented high level of regioselectivities (up to 96%) in the intermolecular crossed acyloin condensations of various aromatic aldehydes with acetaldehyde was realized by an appropriate choice of N-heterocyclic carbene catalysts.

We have shown that prothrombin kringle-2 (pKr-2), a domain of human prothrombin distinct from thrombin could activate cultured rat brain microglia in vitro. However, little is known whether pKr-2-induced microglial activation could cause neurotoxicity on dopaminergic (DA) neurons in vivo. To address this question, pKr-2 was injected into the rat substantia nigra (SN). Tyrosine hydroxylase (TH) immunohistochemistry experiments demonstrate significant loss of DA neurons seven days after injection of pKr-2. In parallel, pKr-2-activated microglia were detected in the SN with OX-42 and OX-6 immunohistochemistry. Reverse transcription PCR and double-label immunohistochemistry revealed that activated microglia in vivo exhibit early and transient expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and several proinflammatory cytokines. The pKr-2-induced loss of SN DA neurons was partially inhibited by the NOS inhibitor N(G)-nitro-L-arginine methyl ester hydrochloride, and the COX-2 inhibitor DuP-697. Extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase were activated in the SN as early as 1 hr after pKr-2 injection, and localized within microglia. Inhibition of these kinases led to attenuation of mRNA expression of iNOS, COX-2 and several proinflammatory cytokines, and rescue of DA neurons in the SN. Intriguingly, following treatment with pKr-2 in vitro, neurotoxicity was detected exclusively in co-cultures of mesencephalic neurons and microglia, but not microglia-free neuron-enriched mesencephalic cultures, indicating that microglia are required for pKr-2 neurotoxicity. Our results strongly suggest that microglia activated by endogenous compound(s), such as pKr-2, are implicated in the DA neuronal cell death in the SN., ((c) 2009 Wiley-Liss, Inc.)

Background: Epigenetic alterations such as DNA methylation and histone modification play important roles in carcinogenesis. It has been recently suggested that global histone modification patterns are independent predictors of cancer recurrence. In this study, we used immunohistochemistry to evaluate the patterns of histone H3 and H4 acetylation and trimethylation in gastric adenocarcinomas., Methods: Double 2-mm core tissue microarrays were made from 261 paraffin-embedded gastric adenocarcinoma samples and examined by immunohistochemistry for histone H3 lysine 9 (H3K9) acetylation and trimethylation, histone H4 lysine 16 acetylation, and histone H4 lysine 20 trimethylation. Sections were graded according to the proportion of tumor cells showing nuclear staining., Results: Trimethylation of H3K9 positively correlated with tumor stage (P = 0.043); lymphovascular invasion (P = 0.029), cancer recurrence (P = 0.043), and higher level of H3K9 trimethylation correlated with a poor survival rate (P = 0.008). Multivariate survival analysis showed that H3K9 trimethylation status is an independent prognostic factor (P = 0.014). After categorizing cases according to the dominant modification pattern, we found that methylation dominance was associated with lymphovascular invasion (P = 0.001), cancer recurrence (P = 0.001), and poor survival rate (P = 0.028). Methylation dominance was also an independent prognostic factor (P = 0.026) in multivariate survival analysis., Conclusion: The pattern of histone modification as detected by immunohistochemistry may be useful as a predictor for the recurrence of cancer and may be an independent prognostic factor in gastric adenocarcinomas.

Yellow seed is one of the most important traits of Brassica napus L. Efficient selection of the yellow-seed trait is one of the most important objectives in oilseed rape breeding. Two recombinant inbred line (RIL) populations (RIL-1 and RIL-2) were analyzed for 2 years at 2 locations. Four hundred and twenty SSR, RAPD, and SRAP marker loci covering 1744 cM were mapped in 26 linkage groups of RIL-1, while 265 loci covering 1135 cM were mapped in 20 linkage groups of RIL-2. A total of 19 QTLs were detected in the 2 populations. A major QTL was detected adjacent to the same marker (EM11ME20/200) in both maps in both years. This major QTL could explain 53.71%, 39.34%, 42.42%, 30.18%, 24.86%, and 15.08% of phenotypic variation in 6 combinations (location x year x population). BLASTn analysis of the sequences of the markers flanking the major QTL revealed that the homologous region corresponding to this major QTL was anchored between genes At5g44440 and At5g49640 of Arabidopsis thaliana chromosome 5 (At C5). Based on comparative genomic analysis, the bifunctional gene TT10 is nearest to the homologue of EM11ME20/200 on At C5 and can be considered an important candidate gene for the major QTL identified here. Besides providing an effective strategy for marker-assisted selection of the yellow-seed trait in B. napus, our results also provide important clues for cloning of the candidate gene corresponding to this major QTL.