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Meliasanines A-L, twelve previously unreported tirucallane-type triterpenoids, together with fifteen known ones, have been isolated from the stem bark of Melia toosendan. Their structures and absolute configurations were determined based on HRESIMS, and NMR, combined with calculated ECD and single-crystal X-ray diffraction analyses. Subsequently, all compounds except 10 were evaluated for their inhibitory effect on the production of nitric oxide induced by lipopolysaccharide in RAW264.7 macrophage cells. The results indicated that seven compounds (1, 13, 14, 16, 20, 22, and 23) exhibited significant NO inhibitory effects, with IC 50 values ranging from 1.35 to 5.93 μM, which were more effective than the positive control indomethacin (IC 50  = 13.18 μM). Moreover, the corresponding results of Western blot analysis revealed that meliasanine A (1) can significantly suppress the protein expression of inducible nitric oxide synthase and cyclooxygenase 2 in a concentration-dependent manner. The mechanism study suggested that meliasanine A exerts an anti-inflammatory effect via the nuclear factor-κB signaling pathway by suppressing phosphorylation of P65 and IκBα., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to evaluate the efficacy of decitabine (DAC) and identify factors influencing treatment responses in patients with primary immune thrombocytopenia (ITP) who had failed glucocorticoid therapy. Methods: Clinical data of 61 patients with glucocorticoid-resistant ITP who received DAC therapy (5 mg·m(-2)·d(-1)×3 d via intravenous infusion) for at least three cycles with 3-4-week intervals at the Department of Hematology, Qilu Hospital of Shandong University, from November 2015 to June 2021 were analyzed retrospectively. Results: The 61 patients comprised 20 males and 41 females, with a median age of 45 years (range: 15-81 years). Among them, 43 patients were glucocorticoid-dependent (glucocorticoid-dependent group), while 18 patients were glucocorticoid-resistant (glucocorticoid-resistant group). Following DAC treatment, 12 patients (19.67% ) achieved complete response (CR), and 16 patients (26.23% ) exhibited response (R), resulting in an overall response (OR) rate of 45.90% (28/61). Comparison between the OR group ( n =28) and the non-response (NR) group ( n =33) revealed significant differences in responses to glucocorticoids (dependent or resistant) and platelet counts before treatment ( χ (2)=8.789, P =0.003; z =-2.416, P =0.016). The glucocorticoid-dependent group showed higher platelet counts than the glucocorticoid-resistant group after the second and third cycles of DAC treatment ( P =0.032, 0.024). Moreover, the OR rates after the first, second, and third cycles of DAC treatment in the glucocorticoid-dependent group were all higher than those in the glucocorticoid-resistant group ( P =0.042, P =0.012, P =0.029). A significant correlation was observed between glucocorticoid dependence and responses to DAC treatment ( OR =9.213, 95% CI 1.937-43.820, P =0.005) . Conclusion: DAC demonstrates definitive efficacy with mild adverse effects in a subset of patients with glucocorticoid-resistant primary ITP. Glucocorticoid dependence and higher platelet counts before treatment are associated with a favorable response to DAC therapy.

Extracellular signal-regulated kinase 1/2 (ERK1/2) is a serine/threoninekinase involved in the signal transduction cascade of Ras-Raf-mitogen-activated protein kinase (MEK)-ERK.It participates in the cell growth,proliferation and even invasion by regulating gene transcription and expression.The occurrence of a variety of diseases such as lung cancer,liver cancer,ovarian cancer,cervical cancer,endometriosis,and preeclampsia,as well the metastasis and disease progression,is closely associated with the regulation of cell invasion by ERK1/2 signaling pathway.Therefore,exploring the regulation of ERK1/2 signaling on cell invasion and its role in pathogenesis of diseases may help to develop more effective treatment schemes.This article introduces recent progress in the regulation of ERK1/2 signaling on cell invasion and the role of such regulation in diseases,with a view to give new insights into the clinical treatment of ERK 1/2-related diseases.

Objective: To investigate the effects of DUSP1 on the hippocampal injury of young rats with epilepsy (EP) through mediating ERK1/2 signaling pathway., Methods: Young SD rats were selected and divided into Control, EP, EP + LV-GFP, EP + LV-DUSP1, EP + LV-siDUSP1, and EP + LV-siDUSP1 + U0126 groups. Morris Water Maze Test was used to detect the spatial learning and memory. Nissl staining and TUNEL staining were conducted and the inflammatory factors and oxidative stress-related indicators were also measured. Western blotting was utilized to detect the expression of DUSP1 and ERK1/2 pathway. EP cell model was constructed in vitro to verify the in vivo results., Results: Compared with Control group, young rats in EP group had decreased spatial learning and memory abilities and increased apoptotic rate and decreased number of Nissl positive cells. Besides, the up-regulated levels in inflammatory factors (IL-1β, IL-6), MDA content, and p-ERK1/2/ERK1/2 protein expression, as well as the down-regulated levels in DUSP1 protein expression and SOD content were also observed in EP rats. The EP rats treated with LV-DUSP1 showed obvious improvements regarding the above indicators, while those treated with LV-siDUSP1 had aggravated injury. But the effect of LV-siDUSP1 can be reversed by the treatment with ERK1/2 pathway inhibitor U0126. Further in vitro investigation verified the in vivo results., Conclusion: DUSP1 may ameliorate the oxidative stress and inflammatory injury, as well as improve spatial learning and memory abilities via inhibiting ERK1/2 pathway, eventually playing protective roles in hippocampal injury of young rats with EP., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Rapamycin-insensitive companion of mammalian target of rapamycin (Rictor) protein is a core subunit of mammalian target of rapamycin complex 2, and is associated with cancer progression. However, the biological function of Rictor in cancer, particularly its clinical relevance in gastric cancer (GC) remains largely unknown., Methods: Rictor expression and its association with clinicopathologic characteristics in GC were analyzed by immunohistochemistry. Effect of Rictor and Caveolin-1 (Cav 1) on GC cells apoptosis was evaluated via overexpression experiment in vitro . Mechanisms of Rictor and Cav 1 in GC were explored through overexpression and knockdown, by immunofluorescence and western blot analyses., Results: Rictor was upregulated in GC, and mainly located in the cytoplasm of cancer cells. Moreover, higher Rictor levels were associated with worse prognosis. Rictor could inhibit GC cell apoptosis and promote cell growth in vitro . The results of immunofluorescence revealed that Cav 1 localized in GC cell membrane but did not co-localize with Rictor. Further, Rictor regulated apoptosis-related proteins, long non-coding RNAs and also activated cellular signaling, thereby positively regulating Cav 1 expression. This effect was attenuated by the Akt inhibitor ly294002. Cav 1 did not significantly affect the ability of Rictor to inhibit tumor cell apoptosis., Conclusions: Rictor is upregulated in GC and associated with worse prognosis. It inhibits tumor apoptosis and activates Cav 1 through the Akt signaling pathway to inhibit the apoptosis of GC cells. Rictor is, therefore, a promising prognostic biomarker and possible therapeutic target in GC patients., 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 © 2021 Cao, Min, Liu, Tian, Jiang, Liu, Shao, Cheng, Zhu, Guo and Li.)

It has been proven a close relationship between intestinal microbiota and hypertension. Valsartan is a widely used ARB antihypertensive drug; so far, the effect of valsartan on intestinal microbiota remains largely unexplored. Herein, we evaluated the composition, structure and metabolites of intestinal microbiota of spontaneously hypertensive rats (SHRs) after valsartan administration. In the present study, valsartan administration decreased intestinal microbiota diversity, altered gut microbiota composition, leading to 192 unique OTUs deficiency ( vs WKY rats) and 10 unique OTUs deficiency ( vs SHRs) and did not prove impaired intestinal mucosal barriers. Valsartan decreased the production of isobutyric acid and isovaleric acid in SCFAs. Our findings revealed valsartan administration induced far-reaching and robust changes to the intestinal microbiota of SHRs and provided a better understanding of the relationship between efficacy of valsartan and gastrointestinal tract reaction., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Aims: To assess the effectiveness of renin-angiotensin-aldosterone system (RAAS) inhibitors, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) separately to prevent all-cause mortality, myocardial infarction (MI), stroke and heart failure (HF) in patients with diabetes considering the number needed to treat (NNT) and minimal clinical effect (MCE)., Methods: Data from 17 morbidity-mortality trials in patients with diabetes were used to calculate NNTs and evaluate MCE to prevent all-cause mortality, myocardial infarction, stroke, and heart failure., Results: A total of 17 trials involving 42,037 patients were included in this meta-analysis. Mean follow-up was 3.7 years. ACEIs significantly reduced the risk of all-cause mortality, MI and HF; the corresponding mean NNTBs were 48, 62 and 78, respectively, but ARBs were only associated with a reduction in heart failure. The clinical significance assessment of the included trials indicated that most of the statistically significant trial results had no definitive clinical significance, and only some of them had possible clinical significance., Conclusions: Among patients with diabetes, ACEIs reduced all-cause mortality, MI and HF, whereas ARBs could only prevent HF. However, none of the results of these trials had clear clinical significance, and most had only possible clinical significance., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The combination of Eucommia ulmoides and Tribulus terrestris (ET) has been widely utilized in clinical practice for thousands of years, but the mechanism underlying its efficacy has not been elucidated to date. This study attempted to investigate the role played by the intestinal microbiota and fecal metabolism in the response of elderly spontaneous hypertensive rats (SHRs) to ET administration as a treatment for hypertension. Fourteen male spontaneously hypertensive rats (SHRs, 18 months old) were randomly divided into an ET group and an SHR group, and 7 Wistar-Kyoto (WKY) rats of the same age were employed as the control group. The ET group was intragastrically administered 1.0 g/kg/d ET for 42 days, and SHRs and WKY rats were administered an equal amount of normal saline intragastrically. The intestinal microbiota and fecal metabolism were analyzed by 16S rRNA sequencing and the GC-MS (gas chromatography-mass spectrometry)/MS assay. ET treatment decreased blood pressure steadily, improved the colonic tissue morphology, and changed the structure and composition of the imbalanced microbiota in SHRs. Specifically, ET treatment increased the abundance of Eubacterium , which might be one of the target microbes for ET, and had a negative correlation with the levels of α -tocopherol, chenodeoxycholic acid, and deoxycholic acid according to the Spearman correlation analysis. The change in the intestinal microbiota affected the fecal metabolic pattern of SHRs. Eight potential biomarkers were determined to be primarily enriched in ABC transporters, phenylalanine metabolism, central carbon metabolism in cancer, purine metabolism, and protein digestion and absorption. The correlation analysis demonstrated that the abundance of Eubacterium and the decreased levels of α -tocopherol, chenodeoxycholic acid, and deoxycholic acid in the ET group were highly correlated. Our results suggest that ET has a good antihypertensive effect, which may be driven by the intestinal microbiota and their beneficial metabolites. The results of this study may help to elucidate the antihypertensive mechanism of ET., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2020 Ying-Zi Qi et al.)

Despite the common application and considerable efforts to achieve precision radiotherapy (RT) in several types of cancer, RT has not yet entered the era of precision medicine; the ability to predict radiosensitivity and treatment responses in tumors and normal tissues is lacking. Therefore, development of genome-based methods for individual prognosis in radiation oncology is urgently required. Traditional DNA sequencing requires tissue samples collected during invasive operations; therefore, repeated tests are nearly impossible. Intra- and inter-tumoral heterogeneity may undermine the predictive power of a single assay from tumor samples. In contrast, analysis of circulating tumor DNA (ctDNA) allows for non-invasive and near real-time sampling of tumors. By investigating the genetic composition of tumors and monitoring dynamic changes during treatment, ctDNA analysis may potentially be clinically valuable in prediction of treatment responses prior to RT, surveillance of responses during RT, and evaluation of residual disease following RT. As a biomarker for RT response, ctDNA profiling may guide personalized treatments. In this review, we will discuss approaches of tissue DNA sequencing and ctDNA detection and summarize their clinical applications in both traditional RT and in combination with immunotherapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Disequilibrium of CD4 + T-cell subpopulations in peripheral blood (PB) of patients with primary immune thrombocytopenia (ITP) has been well established, whereas the profile of CD4 + T-cell subpopulations in bone marrow (BM) remains elusive. In the present study, the frequencies of T helper 22 (Th22), Th17, Th1, Th2, follicular T helper (Tfh) cells and regulatory T cells (Tregs) as well as their effector cytokines in BM and PB from active ITP patients and healthy controls (HCs) were determined. Results showed that the frequencies of Th22, Th17, Th1, and Tfh cells were significantly higher, but Treg number was remarkably lower in BM from ITP patients than from HCs. In the ITP group, it was notable that the numbers of BM Th22, Th17, Th1, Th2, and Tfh cells were significantly elevated compared with the matched PB counterparts, while Treg number in BM was considerably reduced compared with that in PB. In consistence with the BM Th subset pattern, plasma levels of interleukin (IL)-22, IL-17A, and interferon (INF)-γ in BM from ITP patients were significantly increased compared with that from HCs. Therefore, the balance of CD4 + T-cell subsets was disrupted in both BM and PB of ITP patients, suggesting that this might play important roles in the pathophysiological process of ITP., Competing Interests: Competing Interests: The authors declare no conflict of interest. The funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (© The author(s).)

The sustained activation of Angiotensin II (Ang II) induces the remodelling of neurovascular units, inflammation and oxidative stress reactions in the brain. Long non-coding RNAs (lncRNAs) play a crucial regulatory role in the pathogenesis of hypertensive neuronal damage. The present study aimed to substantially extend the list of potential candidate genes involved in Ang II-related neuronal damage. This study assessed apoptosis and energy metabolism with Annexin V/PI staining and a Seahorse assay after Ang II exposure in SH-SY5Y cells. The expression of mRNA and lncRNA was investigated by transcriptome sequencing. The integrated analysis of mRNA and lncRNAs and the molecular mechanism of Ang II on neuronal injury was analysed by bioinformatics. Ang II increased the apoptosis rate and reduced the energy metabolism of SH-SY5Y cells. The data showed that 702 mRNAs and 821 lncRNAs were differentially expressed in response to Ang II exposure (244 mRNAs and 432 lncRNAs were upregulated, 458 mRNAs and 389 lncRNAs were downregulated) (fold change ≥ 1.5, P < 0.05). GO and KEGG analyses showed that both DE mRNA and DE lncRNA were enriched in the metabolism, differentiation, apoptosis and repair of nerve cells. This is the first report of the lncRNA-mRNA integrated profile of SH-SY5Y cells induced by Ang II. The novel targets revealed that the metabolism of the vitamin B group, the synthesis of unsaturated fatty acids and glycosphingolipids are involved in the Ang II-related cognitive impairment. Sphingolipid metabolism, the Hedgehog signalling pathway and vasopressin-regulated water reabsorption play important roles in nerve damage.

Carbon nanotube (CNT) thin-film transistor (TFT) is a promising candidate for flexible and wearable electronics. However, it usually suffers from low semiconducting tube purity, low device yield, and the mismatch between p- and n-type TFTs. Here, we report low-voltage and high-performance digital and analog CNT TFT circuits based on high-yield (19.9%) and ultrahigh purity (99.997%) polymer-sorted semiconducting CNTs. Using high-uniformity deposition and pseudo-CMOS design, we demonstrated CNT TFTs with good uniformity and high performance at low operation voltage of 3 V. We tested forty-four 2-µm channel 5-stage ring oscillators on the same flexible substrate (1,056 TFTs). All worked as expected with gate delays of 42.7 ± 13.1 ns. With these high-performance TFTs, we demonstrated 8-stage shift registers running at 50 kHz and the first tunable-gain amplifier with 1,000 gain at 20 kHz. These results show great potentials of using solution-processed CNT TFTs for large-scale flexible electronics.

Melanosis developed in shrimp ( Penaeus vannamei ) is mainly initiated by polyphenoloxidase (PPO), thus understanding of the characteristics of PPO in shrimp is important for controlling the melanosis of shrimp. The shrimp cephalothorax turns black most rapidly amongst all the tissues during the chilled storage. Crude PPO extracted from this cephalothorax has an optimal pH of 6.0 and an optimal temperature of 50 °C. PPO is relatively stable under neutral and weak alkaline conditions (pH 5.5-9.0) and the temperature range of 25-35 °C. The kinetic parameters K m and V max were recorded as 3.02 mM and 54.3 U/mg of protein, respectively, using L-Dopa as a substrate. The molecular weight of PPO was estimated as 200-220 kDa by an activity staining test. A hydroxypyridinone derivative, 5-hydroxy-1-octyl-4-oxo-1,4-dihydropyridine-2-carbaldehyde O-ethyl oxime, was demonstrated to efficiently inhibit the PPO, indicating that this compound might find application as a shrimp preservative., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest.

Objective: To screen the changes of microRNA (miRNA) expression profiles in lung tissues of early silicosis rats, and provide a basis for functional analysis of differential microRNA. Methods: SPF Wistar male rats were randomly divided into a negative control group and SiO(2)-exposed groups, with 30 rats in each group. The model of silicosis in rats was established by intratracheal instillation of 1 ml SiO(2) suspension, and the control rats were treated with 1mL in the same way to sterilize normal saline. The lung tissues of two group were collected at the 1, 7, 14, 21, 28 d after SiO(2)-exposed. Three of the rat lung tissues were used for pathological observation, and the other three were used to screen differentially expressed miRNAs in lung tissue by miRNA microarray technology. miRNA chip screening and RT-qPCR were used to verify the expression levels of miRNA-423-5p and miRNA-26a-5p in the two groups. miRNA-423-5p and miRNA-26a-5p are predicted by target genes and analyzed by GO (gene ontology) enrichment analysis and KEGG (kyoto encyclopedia of genes and genomes) pathway analysis. Results: In the control group, the inflammatory response of lung tissue 21 and 28 days was significantly reduced compared with 1, 7 and 14 days, and the inflammatory cells infiltrated in the lung tissue of the SiO(2)-exposed rats. The rats in the control group had a small amount of collagen at 21 and 28 days, but a large amount of collagen fiber deposition began to appear in the lung tissue of rats exposed to SiO(2) after 21 days. Compared with the control group, the expression levels of micro RNA-423-5p was significantly up-regulated and the expression of microRNA-26a-5p was significantly down-regulated in the SiO(2)-exposed rats lung tissues dust at different time points ( P <0.05) . Conclusion: The up-regulation of miRNA-423-5p and the down-regulation of miRNA-26a-5p in lung tissues of early silicotic rats may be related to the occurrence and development of early silicosis.

A new class of hybrids with the unique electrocatalytic nanoarchitecture of Fe 1- x S anchored on Fe 3 C-encapsulated and N-doped carbon nanotubes (Fe 1- x S/Fe 3 C-NCNTs) is innovatively synthesized through a facile one-step carbonization-sulfurization strategy. The efficient synthetic protocols on phase structure evolution and dynamic decomposition behavior enable the production of the Fe 1- x S/Fe 3 C-NCNT hybrid with advanced structural and electronic properties, in which the Fe vacancy-contained Fe 1- x S showed the 3d metallic state electrons and an electroactive Fe in +2/+3 valence, and the electronic structure of the CNT was effectively modulated by the incorporated Fe 3 C and N, with the work function decreased from 4.85 to 4.63 eV. The meticulous structural, electronic, and compositional control unveils the unusual synergetic catalytic properties for the Fe 1- x S/Fe 3 C-NCNT hybrid when developed as counter electrodes (CEs) for dye-sensitized solar cells (DSSCs), in which the Fe 3 C- and N-incorporated CNTs with reduced work function and increased charge density provide a highway for electron transport and facilitate the electron migration from Fe 3 C-NCNTs to ultrahigh active Fe 1- x S with the electron-donating effect, and the Fe vacancy-enriched Fe 1- x S nanoparticles exhibit ultrahigh I 3 - adsorption and charge-transfer ability. As a consequence, the DSSC based on the Fe 1- x S/Fe 3 C-NCNT CE delivers a high power conversion efficiency of 8.67% and good long-term stability with a remnant efficiency of 8.00% after 168 h of illumination, superior to those of traditional Pt. Furthermore, the possible catalytic mechanism toward I 3 - reduction is creatively proposed based on the structure-activity correlation. In this work, the structure engineering, electronic modulation, and composition control opens up new possibilities in constructing the novel electrocatalytic nanoarchitecture for highly efficient CEs in DSSCs.

Background: Long noncoding RNAs (lncRNAs) play a key role in the development of endothelial dysfunction. However, few lncRNAs associated with endothelial dysfunction after atorvastatin administration have been reported., Methods: In the present study, differentially expressed (DE) genes in ox-LDL versus control and ox-LDL + atorvastatin versus control were detected. Bioinformatics analysis and integrated analysis of mRNAs and lncRNAs were conducted to study the mechanisms of endothelial dysfunction after atorvastatin administration and to explore the regulation functions of lncRNAs., Results: Here, 532 DE mRNAs and 532 DE lncRNAs were identified (among them, 195 mRNAs and 298 lncRNAs were upregulated, 337 mRNAs and 234 lncRNAs were downregulated) after ox-LDL treatment for 24 hours (fold change ≥2.0, P < .05). After ox-LDL treatment following atorvastatin administration, 750 DE mRNAs and 502 DE lncRNAs were identified (among them, 149 mRNAs and 218 lncRNAs were upregulated and 601 mRNAs and 284 lncRNAs were downregulated). After atorvastatin administration, 167 lncRNAs and 262 mRNAs were still DE. Q-PCR validated the results of microarrays., Conclusion: Chronic inflammatory response, nitric oxide biosynthetic process, microtubule cytoskeleton, cell proliferation and cell migration are regulated by lncRNAs, which also participated in the mainly molecular function and biological processes underlying endothelial dysfunction. Atorvastatin partly improved endothelial dysfunction, but the aspects beyond recovery were mainly concentrated in cell cycle, mitosis, and metabolism. Further exploration is required to explicit the mechanism by which lncRNAs participate in endothelial dysfunction.

Objective: To discuss the effect of psychological nursing based on relaxation training for the psychological state in patients with impatced third molar removal surgery. Methods: A total of one hundred patients with impacted third molar removal surgery were selected from June 2015 to June 2017 in People's Liberation Army No. 105 hospital. According to the nursing method, all patients were divided into psychological intervention group and the control group, 50 cases in each group, the control group was given routine nursing intervention and the psychological intervention group was given psychological nursing intervention based on relaxation training. Results: The after intervention Corah ' s modified dental anxiety scale (6.3±1.2), Stouthard dental fear scale (62.9±6.5) scores and heart rate [(76.4±5.2) bpm], systolic blood pressure [(102.5±6.3) mmHg], diastolic blood pressure [(75.3±3.1) mmHg] levels of psychological group were significantly lower than those of the control group. The once removal success rate, intraoperative relaxation sense rate of psychological group were significantly higher than those of the control group, the teeth extraction time of psychological group was significantly lower than that of the control group, the difference was statistically significant ( P =0.013, P =0.003). Conclusions: Psychological nursing intervention based on relaxation training can effectively improve the mental state and stress state of patients with impacted third molar removal surgery, which is beneficial to the process of the surgery.

A range of hydroxypyridinone derivatives were synthesized starting from kojic acid. Among them, 10 and 11 were found to possess the strongest inhibitory effect on monophenolase activity of mushroom tyrosinase, having IC 50 values of 2.04 and 1.60μM, respectively. The IC 50 values of 10 and 11 for the inhibition of diphenolase activity of mushroom tyrosinase were determined as 13.89 and 7.99μM, respectively. Investigation of the inhibitory mechanism of these two compounds indicated that the inhibition was reversible and of a competitive-uncompetitive mixed type. The K I and K IS values of 10 were determined to be 24.84 and 32.54μM, respectively, and the corresponding values for 11 being 18.07 and 21.34μM, respectively. The effect of 11 on the browning process of fresh-cut apples was evaluated by measuring the color change and browning index. The results indicated that 11 had a significant effect on controlling the browning of fresh-cut apple slices., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In order to improve the antioxidant and antimicrobial abilities, hydroxamated degraded polysaccharides from Enteromorpha prolifera (HCDPE) were prepared from the corresponding carboxymethylated degraded polysaccharides (CDPE). HCDPE was characterized by FT-IR. The weight-average molecular weight of HCDPE was determined as 55.4kDa. The in vitro antioxidant activity of HCDPE was evaluated by determining the radical (1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl and superoxide anion radicals) scavenging abilities and total antioxidant activity. It was found that DPPH radical scavenging ability and total antioxidant activity of HCDPE were significantly improved compared to those of CDPE. The inhibitory effects of polysaccharides against the five bacterial strains (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella spp.) were also evaluated by bacterial inhibition zone and minimum inhibitory concentration (MIC) assays. The results indicated that CDPE and HCDPE possess marked antimicrobial ability, while such an effect was not observed for the crude polysaccharides (PE) and the degraded polysaccharides (DPE)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Essentials M1/M2 imbalance is involved in many autoimmune diseases, and could be restored. The expressions and functions of M1 and M2 were investigated in an in vitro culture system. A preferred M1 polarization is involved in the pathogenesis of immune thrombocytopenia (ITP). High-dose dexamethasone or all-trans-retinoic acid restores M1/M2 balance in ITP patients., Summary: Background Immune thrombocytopenia (ITP) is an autoimmune disorder. Deficiency of immune tolerance in antigen-presenting cells and cross-communication between antigen-presenting cells and T cells are involved in the pathogenesis of ITP. Macrophages can polarize into proinflammatory M1 or anti-inflammatory M2 phenotypes in response to different environmental stimuli, and have diverse immunologic functions. Objectives To investigate the M1/M2 imbalance in ITP and whether high-dose dexamethasone (HD-DXM) or all-trans-retinoic acid (ATRA) could restore this imbalance. Methods The numbers of M1 and M2 macrophages in the spleens of ITP patients and patients with traumatic spleen rupture were analyzed by immunofluorescence. Monocyte-derived macrophages were cultured and induced with cytokines and drugs. The expression of M1 and M2 markers and functions of M1 and M2 macrophages before and after modulation by HD-DXM or ATRA were evaluated with flow cytometry and ELISA. Results There was preferred M1 polarization in ITP spleens as compared with healthy controls. Monocyte-derived macrophages from ITP patients had increased expression of M1 markers and impaired immunosuppressive functions. Either HD-DXM or ATRA corrected this imbalance by decreasing the expression of M1 markers and increasing the expression of M2 markers. Moreover, HD-DXM-modulated or ATRA-modulated macrophages suppressed both CD4 + and CD8 + T-cell proliferation and expanded CD4 + CD49 + LAG3 + type 1 T-regulatory cells. HD-DXM or ATRA modulated macrophages to shift the T-cell cytokine profile towards Th2. Treating patients with HD-DXM or ATRA revealed that macrophages induced from responders showed a predominant M2-like phenotype and immunosuppressive function. Conclusions Aberrant macrophage polarization is involved in the pathogenesis of ITP. Either HD-DXM or ATRA is able to correct this imbalance., (© 2017 International Society on Thrombosis and Haemostasis.)

Multiple myeloma (MM) is a malignancy characterized by plasma cell hyperplasia. The majority of patients with MM suffer from mortality due to tumor recurrence and metastasis, which has become an emerging clinical problem. Transforming growth factor β1 (TGFβ1) has been implicated in tumor metastasis; however, its role in RPMI 8226 cells remains to be elucidated. In the present study, RPMI 8226 cells were treated with various concentrations of SB431542, a TGFβ1 inhibitor, for 12, 24 and 48 h. RPMI 8226 cells were transfected with lentiviral-TGFβ1 vectors to overexpress TGFβ1. Cell proliferation rate was subsequently determined by cell-counting kit-8 assay and cell invasion was assessed by Transwell assay. Expression of TGFβ1, SMAD family member 2 (Smad2) and matrix metallopeptidase 3 (MMP3) were analyzed by western blotting. The results demonstrated that cell proliferation and invasion of RPMI 8226 cells was significantly inhibited by SB431542 (P<0.05). SB431542 was able to significantly downregulate the expression of TGFβ1, phosphorylated (p)-Smad2 and MMP3; however, the overexpression of TGFβ1 significantly upregulated the expression of TGFβ1, p-Smad2 and MMP3. In conclusion, SB431542 reduced cell invasion in RPMI 8226 cells, and this effect may be mediated via the TGFβ1/Smad2/MMP3 signaling pathway.

Hydrothermal treatment of nickel acetate and phosphoric acid aqueous solution followed with a carbothermal reduction assisted phosphorization process using sucrose as the carbon source for the controlled synthesis of Ni x P y /C was successfully realized for the first time. The critical synthesis factors, including reduction temperature, phosphorus/nickel ratio, pH, and sucrose amount were systematically investigated. Remarkably, the carbon serves as a reducer and plays a determinative role in the transformation of Ni 2 P 2 O 7 into Ni 2 P/C. The synthesis strategy is divided into four distinguishable stages: (1) hydrothermal preparation of Ni 3 (PO 4 ) 2 ·8H 2 O precursor for stabilizing P sources; (2) dimerization of Ni 3 (PO 4 ) 2 ·8H 2 O into more thermal stable Ni 2 P 2 O 7 amorphous phase along with the generation of NiO; (3) carbothermal reduction and phosphidation of NiO into Ni x P y (0 ≤ y/x ≤ 0.5); and (4) further phosphidation of mixed-phase Ni x P y and carbothermal reduction of Ni 2 P 2 O 7 into single-phase Ni 2 P. The resultant Ni 2 P, the highly active phase in electrocatalysis, was applied as counter electrode in a dye-sensitized solar cell (DSSC). The DSSC based on Ni 2 P with 10.4 wt.% carbon delivers a power conversion efficiency of 9.57%, superior to that of state-of-the-art Pt-based cell (8.12%). The abundant Ni δ+ and P δ- active sites and the metal-like conductivity account for its outstanding catalytic performance.

The researches on chlamydia in recent years show that chlamydia bacteriophage may be a potential and effective means to solve the clinical infection of chlamydia trachomatis (Ct). We investigated the biological effect of chlamydiaphage phiCPG1 capsid protein Vp1 on Ct both in McCoy cells and genital tract of mice. Different concentrations of Vp1 were co-incubated with Ct E serotype strain in McCoy cells. Female BALB/c mice were used to establish Ct E strain-induced urogenital infection model. They were randomly divided into five groups and given different treatments on the fifth day after Ct inoculation. Animals in groups 1 and 2 were given 30 μL different concentrations of Vp1 in the genital tract respectively, those in group 3 were intramuscularly injected with 30 μL Vp1, those in the infected group did not receive any intervention, and those in the control group received 30 μL PBS in the genital tract. The vaginal discharge was collected to identify the live chlamydia by cell culture and gene fragment by real time PCR different days after infection. Inhibition rate of 100 μg/mL and 50 μg/mL Vp1 proteins against Ct E strain in the McCoy cell cultures was 91% and 79% respectively. The number of intracellular Ct inclusion in the McCoy cells co-cultured with vaginal discharge of group 1 and group 2 was less than in the infected group, and that in group 1 was less than in group 2, on the 7th day after Ct inoculation. Real-time PCR showed that chlamydia concentration of the vaginal discharge in group 2 was lower than in the infected group, and that in group 1 was lower than in group 2 on the 10th day. It was suggested that Vp1 capsid proteins had inhibitory effect on the proliferation of Ct serovar E strain in cell culture and mouse genital tract.

Syphilis is a sexually transmitted disease caused by Treponema pallidum. Minocycline, a representative tetracycline derivative, has the greatest antimicrobial activity among all tetracyclines. There are few reports about treating syphilis with minocycline because there is a lack of efficacy data from controlled trials. We compared the rates of serological cure in patients with early syphilis who were treated with minocycline or benzathine penicillin G (BPG).During the study period, a total of 40 syphilis patients received the BPG treatment, which was a single intramuscular dose of 2.4 million units of BPG, and 156 patients were treated with minocycline; 77 patients were placed in the 2-week, standard minocycline therapy group and received 100 mg of minocycline orally, twice daily for 14 days, and 79 patients were placed in the 4-week, lengthened minocycline therapy group and received 100 mg of minocycline orally, twice daily for 28 days. The outcome of interest was the rate of serological cure in these patients.At the end of the 2-year follow-up, the serological cure rate of the 4-week, lengthened minocycline therapy group (87.34%) was higher than that of both the 2-week, standard minocycline therapy group (72.73%) and the BPG treatment group (77.50%). In addition, the curative effect of the 4-week, lengthened minocycline therapy was significantly greater than that of the 2-week, standard minocycline therapy in patients who were aged >40 years; exhibited an initial rapid plasma reagin titer ≥1: 32; or exhibited secondary syphilis (P = 0.000, 0.008, 0.000; <0.05).Minocycline appears to be an effective agent for treating early syphilis, especially when applied as a 4-week, lengthened therapy., Competing Interests: The authors have no conflicts of interest to disclose.

Developing low-cost, durable, and highly catalytic counter electrode (CE) materials based on earth-abundant elements is essential for dye-sensitized solar cells (DSSCs). In this study, we report a highly active nanostructured compositional material, TiOPC, which contains titanium, oxygen, phosphorus, and carbon, for efficient CE in I 3 - /I - electrolyte. The TiOPC nanocomposites are prepared from carbon thermal transformation of TiP 2 O 7 in an atmosphere of nitrogen at high temperature, and their catalytic performance is regulated by changing the carbon content in the nanocomposites. The TiOPC with appropriate 24.6 wt % carbon and porous structure exhibits an enhanced electrocatalytic activity in the reduction of I 3 - , providing a short-circuit current density of 16.64 mA cm -2 , an open-circuit potential of 0.78 V, and an energy conversion efficiency of 8.65%. The photovoltaic performance of TiOPC CE-based DSSC is even superior to that of a Pt CE-based cell (13.80 mA cm -2 , 0.79 V, and 6.66%). The enhanced catalytic activity of TiOPC is attributed to the presence of predominant Ti-O-P-C structure along with the continuous conductive carbon network and the porous structure.

Development of novel nano-drug delivery systems (NDDS) that can transport anticancer drugs into cell nuclei is still a highly desirable strategy for reversing multi-drug resistance (MDR) in cancer therapy. Herein, we designed and prepared a novel NDDS, designated S@L NPs, in which several smaller nanoparticles are contained within a larger nanoparticle. Our S@L NPs (CS/PAA/VP-16@TPGS/PLGA NPs) possess a structure in which smaller nanoparticles (Chitosan-Poly(acrylic acid) nanoparticles, CS/PAA NPs) containing the drug etoposide (VP-16) are loaded within a larger nanoparticle (Vitamin E d-a-tocopheryl polyethylene glycol 1000 succinate-modified poly(lactic-co-glycolic acid) nanoparticles, TPGS/PLGA NPs). The system utilizes intracellular pH gradients to achieve pH-sensitive sequential release within different intracellular domains of MDR cells. S@L NPs could be triggered to degrade and release CS/PAA/VP-16 NPs in the acid environment of the cytosol, endosomes or lysosomes, and CS/PAA/VP-16 NPs were capable of entering the nucleus through nucleopores. It is significant that CS/PAA/VP-16 NPs exhibit disaggregation in the alkaline environment of the nucleus and thereby release the contained anticancer drug. Further mechanistic studies showed that CS/PAA/VP-16 NPs escaped retention and degradation within lysosomes and protected the drug from P-glycoprotein-induced efflux. Simultaneously, S@L NPs enhanced the anticancer effect of the loaded drug by inducing autophagy and apoptosis of MDR cells. This novel NDDS may provide a promising platform for nuclear drug delivery for reversing MDR., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature cells and natural inhibitors of adaptive immunity. In this study, the MDSC population was evaluated in adult patients with primary immune thrombocytopenia (ITP), where cell-mediated immune mechanisms are involved in platelet destruction. Our data demonstrated that both the numbers and suppressive functions of MDSCs were impaired in the peripheral blood and spleens of patients with ITP compared with healthy control patients. High-dose dexamethasone (HD-DXM) treatment rescued MDSC numbers in patients with ITP. And DXM modulation promoted the suppressive function of MDSCs induced in vitro. Moreover, the expression of interleukin 10 and transforming growth factor β was significantly upregulated in DXM-modulated MDSCs compared with the unmodulated cultures. DXM-modulated MDSCs inhibited autologous CD4(+)T-cell proliferation and significantly attenuated cytotoxic T lymphocyte-mediated platelet lysis, further indicating enhanced control over T-cell responses. Elevated expression of the transcription factor Ets1 was identified in DXM-modulated MDSCs. Transfection of Ets-1 small interfering RNA efficiently blocked regulatory effects of MDSCs, which almost offset the augmentation of MDSC function by DXM. Meanwhile, splenocytes from CD61 knockout mice immunized with CD61(+)platelets were transferred into severe combined immunodeficient (SCID) mouse recipients (C57/B6 background) to induce a murine model of severe ITP. We passively transferred the DXM-modulated MDSCs induced from bone marrow of wild-type C57/B6 mice into the SCID mouse recipients, which significantly increased platelet counts in vivo compared with those receiving splenocyte engraftment alone. These findings suggested that impaired MDSCs are involved in the pathogenesis of ITP, and that HD-DXM corrected MDSC functions via a mechanism underlying glucocorticoid action and Ets1., (© 2016 by The American Society of Hematology.)

Unlabelled: ESSENTIALS: Dysfunctional B-cell-activating factor (BAFF) system is related to many autoimmune diseases. The regulatory functions of BAFF/BAFF receptors were investigated in an in vitro coculture system. Different regulatory roles of BAFF were investigated via different receptors in immune thrombocytopenia. The upregulated BAFF receptors on autoreactive lymphocytes lead to their hypersensitivity to BAFF., Background: The pathogenesis of immune thrombocytopenia (ITP) remains enigmatic. B-cell-activating factor (BAFF) and its receptors (BAFF receptor [BAFF-R], transmembrane activator and calcium modulator and cyclophilin ligand interactor [TACI], and B-cell maturation antigen) play central roles in the integrated homeostatic regulation of lymphocytes., Objectives: To investigate the pathologic roles of BAFF receptors in regulating the bioactivities of lymphocytes in ITP., Methods: An in vitro culture system was established by stimulating CD14(-) peripheral lymphocytes with platelet-preloaded dendritic cells in the presence of recombinant human BAFF (rhBAFF; 20 ng mL(-1)). The functions of BAFF receptors were specifically blocked with blocking antibodies., Results: BAFF-R, besides prolonging the survival of B cells in both patients and healthy controls, prominently promoted the survival of CD8(+) T cells and the proliferation of B cells in patients with ITP. TACI, as a positive regulator, not only promoted the proliferation of CD4(+) and CD8(+) T cells, but also significantly enhanced the secretion of interleukin-4 in patients with ITP, but not in controls. Besides revealing the pathologic roles of BAFF receptors, these results also indicate that lymphocytes of patients with ITP have enhanced antiapoptotic or proliferative capacity as compared with those from healthy controls when exposed under similar stimulation of rhBAFF. Further study demonstrated that activated autoreactive B cells and CD4(+) T cells from patients with ITP showed significantly higher expression of BAFF-R or TACI than those from healthy controls., Conclusions: Both BAFF-R and TACI are pathogenic participants in ITP. Their dysregulated expression in patients with ITP may lead to hyperreactivity of activated autoreactive lymphocytes in response to rhBAFF, and thus is highly significant in the pathogenesis of ITP., (© 2016 International Society on Thrombosis and Haemostasis.)

This study shows that Cd induces autophagy in the human's embryonic normal liver cell line (WRL-68). The expression of LC3B-II and the mature cathepsin L were analyzed by Western blotting. The autophagosomes and lysosomes were directly visualized by electron microscopy and confocal microscopy analysis in Cd-exposed WRL-68 cells. In this study, we first found that autophagy induced the activation of lysosomal function in WRL-68 cells. The lysosomal activation was markedly decreased when the cells were co-treated with 3-MA (an inhibitor of autophagy). Secondly, we provided the evidence that the activation of lysosomal function depended on autophagosome-lysosome fusion. The colocalization of lysosome-associated membrane protein-2 (LAMP2) and GFP-LC3 was significantly reduced, when they were treated with thapsigargin (an inhibitor of autophagosome-lysosome fusion). We demonstrated that deletion or blockage of the autophagosome-lysosome fusion process effectively diminished lysosomal activation, which suggests that lysosomal activation occurring in the course of autophagy is dependent on autophagosome-lysosome fusion. Thirdly, we provided evidence that the activation of lysosomal function was associated with lysosomal acid. We investigated the relationship between autophagosome-lysosome fusion and pH in acidic compartments by visualizing fusion process in WRL-68 cells. This suggests that increasing pH in acidic compartments in WRL-68 cells inhibits the autophagosome-lysosome fusion. Finally, we found that the activation of lysosomal function was associated with Ca(2+) stores and the intracellular Ca(2+) channels or pumps were possibly pH-dependent., (Copyright © 2015 John Wiley & Sons, Ltd.)

Objective: Esophageal Squamous Cell Carcinoma (ESCC) is one of the most common human cancers with a particularly high incidence in certain regions of China. Differentially expressed genes (DEG) between the esophageal squamous carcinoma tissues and matched normal esophageal mucosal epithelial tissues can be detected by employing the gene microarray technology. This can aid the analysis of the underlying disease mechanism and can help to identify potentially critical genes as well as related molecular signalling pathways., Materials and Methods: The potentially critical genes and related signal pathways are examined by bioinformatics analysis including Gene Ontology (GO) analysis, pathway analysis and signal transduction networks. Here, we performed microarray analysis with 8 pairs of ESCC and normal esophageal mucosal epithelial tissues., Results: Compared to the control group, 347 and 203 genes were found to be up-regulated and down-regulated in the experimental group, respectively. Based on pathway analysis, 52 and 51 signal transduction pathways were involved in the up-regulated and the down-regulated genes, respectively. SLC27A6, RAB11A, ABCA8, JAM2, HNMT, GSTM1, and CDKN3, which play critical roles in regulating the expression of ESCC, were identified among the key genes involved in the signal transduction networks., Conclusions: Investigation of the mechanism underlying ESCC can provide a direction for the clinical prevention and treatment of ESCC.

Semaphoring is a transmembrane receptor which participates in many cytokine-mediated signal pathways that are closely related to the angiogenesis, occurrence and development of carcinoma. The present study was designed to access the effect of mono-antibody (mAb) guided radioimmunotherapy (RIT) on skin carcinoma and investigate the potential mechanisms. Semaphoring mAb was acquired from mice (Balb/c), purified with rProtein A column; purity, concentration and activity were tested with SDS-PAGE and indirect ELISA; specificity and expression on the cutanuem carcinoma line and tissue were tested by Western blotting; morphology change was assessed by microscopy. MTT assay and colony inhibition tests were carried out to test the influence on the proliferation of tumor cells; Western blotting was also carried out for expression of apoptosis-associated (caspase-3, Bax, Bcl-2) and proliferation-related (PI3K, p-Akt, Akt, p-ERK1/2, ERK1/2) proteins and analyse the change in signal pathways (PI3K/Akt and MEK/ERK). The purity of purified semaphorin mAb was 96.5% and the titer is about 1?106. Western blotting showed semaphoring mAb to have specifically binding stripes with semaphoring b1b2 protein, B16F10, and A431 cells at 39KDa, 100KDa and 130KDa, respectively. Positive expression was detected both in cutanuem carcinoma line and tissue and it mostly located in cell membranes. MMT assay revealed dose-relate and time-relate inhibitory effect of semaphorin mAb on A431 and B16F10. Colony inhibition tests also showed dose-relate inhibitory effects. Western blotting demonstrated the expression of apoptosis and proliferation-related protein and changes in signal pathway. In conclusion, we demonstrated that semaphorin is highly expressed on the tumor cell-surfaces and RIT with semaphorin mAb has effect in inhibiting proliferation and accelerating apoptosis of tumor cells.

The aim of this study was to detect the mRNA expression of tissue factor pathway inhibitor-2 ( TFPI-2) and its methylation in bone marrow mononuclear cells from acute myeloid leukemia (AML) patients and to explore its significance in AML. Bone marrow mononuclear cells were isolated from newly diagnosed AML patients (n = 33), complete remission AML patients (n = 19), relapsed/refractory AML patients (n = 12) and iron deficiency anemia patients (control group, n = 15). Expression of TFPI-2 mRNA was detected with real-time quantitative PCR (RT-PCR) and the methylation of CpG island in its promoter was detected with methylation-specific PCR (MSP). The results showed that the expression of TFPI-2 mRNA in newly diagnosed AML, complete remission AML and relapsed/refractory AML patients was much lower than that in the controls (P < 0.05). Furthermore, its expression in relapsed/refractory AML patients was lower than that in newly diagnosed AML patients (P = 0.006). Compared with complete remission AML patients, the expression of TFPI-2 mRNA in newly diagnosed AML patients was significantly reduced (P = 0.030). The percentage of TFPI-2 promoter methylation in AML patients was 64.63% (42/64). In newly diagnosed AML group, complete remission AML group and relapsed/refractory AML group,the percentages of TFPI-2 promoter methylation were 66.67% (22/33), 52.63% (10/19) and 83.33% (10/12) (P > 0.05), respectively. The optical density ratio of TFPI-2 mRNA expression was 0.165 (0.005-2.099) in methylated AML patients, and 0.597 (0.011-2.787) in unmethylated AML patients (P < 0.05). Methylation of TFPI-2 gene promoter was not detected in control patients. After 2 courses of chemotherapy, the level of TFPI-2 mRNA was much higher in the CR group than that in the non-CR group (P < 0.05). It is concluded that the down-regulation or silence of TFPI-2 gene potentially results from its promoter methylation, and the expression level of TFPI-2 and the methylation status of its promoter may be used as indicators of risk stratification and evaluation of disease progress.

Objective: In this study, we aimed to investigate the expressions of adhesion molecules on human bronchial epithelial cells and neutrophils in co-culture system, assess the effects of puerarin on suppressing these adhesion molecules expressions, and explore the roles of two crucial signal-transduction elements p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor kappa B (NF-κB) in modulating adhesion molecules expressions., Methods: Neutrophils and BEAS-2B cells (one human bronchial epithelial cell line) were co-cultured, and adhesion molecules expressions on cell surface were detected using flow cytometry. The mRNA levels of adhesion molecules were assessed by real-time quantitative polymerase chain reaction (real-time qPCR). Phosphorylated p38 MAPK and inhibitor κB were analyzed by Western blot., Results: In co-culture system, adhesion molecules expressions on BEAS-2B cells and neutrophils were enhanced significantly (P<0.05). Correspondingly, the mRNA levels of adhesion molecules were also increased greatly. Moreover, the pretreatment of peurarin obviously suppressed adhesion molecules expressions on cell surface. Furthermore, phosphorylated p38 MAPK and inhibitor κB in BEAS-2B cells and neutrophils were elevated in co-culture system, but decreased significantly after upon the treatment of peurarin (P<0.05)., Conclusions: Coculture boosted the interactions between human bronchial epithelial cells and neutrophils mimicking airway inflflammation, whereas peurarin decreased the expression of adhesion molecules on cell surface by suppressing the activities of p38 MAPK and NF-κB pathways, and exhibiting its anti-inflflammation activity.

The mitochondrial genome of Hybris subjacens (Neuroptera: Ascalaphidae) is a circular molecule of 15,873 bp in length, containing 37 typical animal mitochondrial genes: 13 protein-coding genes (PCGs), 2 ribosomal RNAs, 22 transfer RNAs and a non-coding AT-rich region. Its gene order and arrangement are identical to the common type found in most insect mitogenomes. All PCGs start with a typical ATN codon except for COI and ND1 which use CTT and TTG as their start codon, respectively; all PCGs terminate in the common stop codon TAA or TAG, except for the COI and ND5 which use single T as their stop codons. The non-coding AT-rich region is 1051 bp long, located between rrnS and tRNA(lle) genes. It contains some structures of repeated motifs and microsatellite-like elements characteristic of the neuropterids.

We sequenced the complete mitochondrial genome (mitogenome) of Cheirotonus jansoni (Coleoptera: Scarabaeidae), an endangered insect species from Southeast Asia. This long legged scarab is widely collected and reared for sale, although it is rare and protected in the wild. The circular genome is 17,249 bp long and contains a typical gene complement: 13 protein-coding genes, 2 rRNA genes, 22 putative tRNA genes, and a non-coding AT-rich region. Its gene order and arrangement are identical to the common type found in most insect mitogenomes. As with all other sequenced coleopteran species, a 5-bp long TAGTA motif was detected in the intergenic space sequence located between trnS(UCN) and nad1. The atypical cox1 start codon is AAC, and the putative initiation codon for the atp8 gene appears to be GTC, instead of the frequently found ATN. By sequence comparison, the 2590-bp long non-coding AT-rich region is the second longest among the coleopterans, with two tandem repeat regions: one is 10 copies of an 88-bp sequence and the other is 2 copies of a 153-bp sequence. Additionally, the A+T content (64%) of the 13 protein-coding genes is the lowest among all sequenced coleopteran species. This newly sequenced genome aids in our understanding of the comparative biology of the mitogenomes of coleopteran species and supplies important data for the conservation of this species.

Thalidomide (THD) is an immunomodulatory agent used to treat immune-mediated diseases. Immune thrombocytopenia (ITP) is an autoimmune disorder in which impaired mesenchymal stem cells (MSCs) are potentially involved. We demonstrated that MSCs in ITP patients had reduced proliferative capacity and lost their immunosuppressive function, which could be corrected with THD treatment. According to the gene profile, the downregulation of caspase-8 and caspase-10, and upregulation of oct3/4 and tgf-β1, may be associated with THD modulation. Dendritic cells (DCs) played an important role in mediating the inhibitory activity of MSCs. To study the functional alteration of DCs elicited by MSCs, we sorted DCs after incubation with MSCs and performed T-lymphocyte reaction assays. The THD-modulated MSCs from ITP patients induced mature DCs to become tolerogenic DCs, whereas unmodulated MSCs had no effect. The induction of tolerogenicity in DCs by MSCs was dependent on the expression of TIEG1 in DCs. The study reveals the inability of MSCs from ITP patients to induce tolerogenic ability in DCs. THD could restore the regulatory effect of MSCs on DCs. These findings will help us understand the pathogenesis of ITP, and with appropriate safeguards, THD may benefit patients with ITP.

Adipokines omentin-1 and adiponectin have been reported to improve insulin resistance. It is known that insulin sensitizers exenatide, avandamet, or diet change from high-fat to normal chow ameliorate metabolic disorders. However, whether these treatments increase omentin-1 levels in high fat-diet animals and the relationship between omentin- 1 and adiponectin remain largely unknown. We investigated the effect of insulin sensitizers exenatide and avandamet, and of dietary change on these adipokine levels, body weight, and insulin sensitivity in diet-induced obese rats. Obesity was induced in rats by high-fat diet feeding for 8 weeks, and then the rats were given exenatide, avandamet and diet change to normal chow, respectively, for additional 8 weeks. Compared to the high-fat control group, exenatide and avandamet treatment significantly induced adipose gene expression and elevated the circulation levels of omentin-1 and adiponectin, whereas they decreased the leptin gene expression and circulation level, which is associated with improvement of systemic insulin sensitivity and the glucose and lipid profile. Notably, there was a significant positive correlation between omentin-1 and adiponectin in the above regimens, suggesting that omentin-1 and adiponectin may contribute to the insulin-sensitizing effect of exenatide and avandamet.

Previous studies have shown that PI3K/GSK-3β/β-catenin signaling pathway plays a vital role in ischemic preconditioning. The present study attempts to evaluate whether PI3K/GSK-3β/β-catenin signaling pathway might be responsible for the cardioprotection in ischemic postconditioning. Male Sprague-Dawley rats underwent 30 min of left anterior descending coronary artery occlusion and 2 h of reperfusion. One hundred twenty rats were randomized into six groups: sham, ischemia/reperfusion (I/R), ischemic postconditioning (Post), 15 μg · kg wortmannin (PI3K inhibitor) plus ischemic postconditioning (Wort + Post), wortmannin plus I/R (Wort + I/R), and 0.6 mg · kg SB216763 (GSK-3β inhibitor) plus I/R (SB + I/R). Wortmannin and SB216763 were administered, respectively, 10 and 5 min before reperfusion. Myocardial infarct size; number of apoptotic cardiomyocytes; total Akt, GSK-3β; phosphorylated Akt, GSK-3β; β-catenin in cytosol and nucleus; and Bcl-2 protein were assessed. It was found that Post and SB + I/R reduced infarct size (32.3% [SD, 2.8%], 32.7% [SD, 2.1%], vs. 53.4% [SD, 3.2%], respectively, P < 0.05) and apoptotic index of cardiomyocytes (23.2% [SD, 1.8%], 23.8% [SD, 1.8%], vs. 47.3% [SD, 5.8%], respectively, P < 0.05); compared with I/R, wortmannin abolished the cardioprotection of ischemic postconditioning. Post and SB + I/R increased phosphorylated Akt, phosphorylated GSK3β, β-catenin in cytosol and nucleus, and Bcl-2 expression versus I/R. These results indicate that ischemic postconditioning could induce myocardial protection via PI3K/GSK-3β/β-catenin signaling pathway, activation of which results in accumulation of β-catenin and upregulation of its target genes Bcl-2.

This study was designed to compare the curative effect, prognosis and safety of different preconditioning regimens for patients who received autologous hematopoietic stem cell transplantation (AHSCT) for malignant lymphoma (ML). The clinical data of 100 ML patients (Sep 1992 to Aug 2010 in 307 Hospital) were retrospectively analyzed, and were divided into two groups by different preconditioning regimens: the high-dose chemotherapy preconditioning group and high-dose chemotherapy/radiotherapy preconditioning group. The overall survival (OS) rate, progress free survival (PFS) rate and adverse effect were analyzed. The results showed that until Feb 2011, the median follow-up was 33.5 months. All patients were engrafted and their hematopoiesis was reconstituted. The median time of WBC recovery up to > 1.0×1.0(9)/L in high-dose chemotherapy preconditioning group and high-dose chemotherapy/radiotherapy preconditioning group were (6.0 ± 0.4) d and (8.2 ± 0.4) d, platelet up to > 20.0×1.0(9)/L in two groups were (7.1 ± 0.8) d and (11.4 ± 2.5) d (P < 0.05). The 3-year OS rate of the two groups were 67.3% and 68.9%. 5-year OS rates of two groups were 62.8% and 60.6%, 10-year OS rates of two groups were 57.6% and 56.2% respectively; 3-year PFS of two group were 63.6% and 63.2%, 5-year of two group were 59.4% and 58.3%, 10-year of two group were 50.8% and 55.3% respectively (P > 0.05). Meanwhile, the incidence of fever, infection, bleeding, secondary cancer between two groups was not significant different (P > 0.05). It is concluded that the hematopoietic reconstitution of high-dose chemotherapy/radiotherapy preconditioning group is later than that of high-dose chemotherapy preconditioning group. However, there is no significant difference in curative effect and prognosis between the two groups.

Background: Immunological mechanisms are increasingly recognized in the progression of myelodysplastic syndrome (MDS). Early-stage MDS (E-MDS) is characterized by autoimmune-mediated myelosuppression whereas late-stage MDS (L-MDS) involves immune evasion, giving dysplastic cells growth potential to progress into acute myeloid leukemia. T-helper (Th) 22 is involved in the pathogenesis of inflammatory autoimmunity and tumorigenesis. The roles of Th22 cells in the pathophysiology of E-MDS and L-MDS remain unsettled., Design and Methods: We studied 37 MDS patients (E-MDS, n = 17; L-MDS, n = 20) and 20 healthy controls to characterize their peripheral blood (PB), as well as 25 MDS patients and 10 healthy controls to characterize their bone marrow(BM). The expression of Interleukin-22 (IL-22), IL-17 or interferon gamma (IFN-γ) was examined in E-MDS, L-MDS patients and controls by flow cytometry. The mRNA expression levels of RAR-related orphan receptor C (RORC), IL-6, tumor necrosis factor alpha (TNF-α) and IL-23 in peripheral blood mononuclear cells (PBMCs) were determined by real-time quantitative polymerase chain reaction. The levels of IL-22 and IL-17 both in PB and BM plasma were examined by enzyme-linked immunosorbent assay., Results: In E-MDS, peripheral Th17 cells were significantly elevated and correlated with peripheral Th22 cells compared with healthy controls and L-MDS. Significantly higher levels of peripheral Th22 expansion, mRNA expression of IL-6, TNF-α and lower level of RORC mRNA expression were observed in L-MDS compared with E-MDS. No statistical difference was found in IL-23 mRNA expression or plasma IL-22, IL-17 levels among E-MDS, L-MDS and controls., Conclusions: Our data demonstrated that L-MDS cohort had increased frequencies of peripheral Th22 cells and higher mRNA expression levels of IL-6 and TNF-α, indicating that Th22 cells along with Th17 cells or not are involved in the dynamic immune responses of MDS.

This study was aimed to investigate the common chromosomal aberrations in chronic lymphocytic leukemia (CLL) and to explore the relationship between these chromosomal aberrations and clinical features of CLL. Sequence-specific DNA probes (D13S25, RB1, p53, ATM) and one centromeric probe CSP12 were applied to detect del(13q14), del(17p13), del(11q22-q23) and trisomy 12 by using interphase fluorescence in situ hybridization (I-FISH). 9 CLL patients with negative conventional cytogenetics or without mitotic figure were enrolled in this study. The threshold was established using 10 controls without hematopoietic malignancies. The results indicated that compared with the established threshold, all of the 9 CLL patients showed cytogenetic abnormalities. The detection using p53 and D13S25 showed positive in 7 cases, positive was observed in 5 cases by using ATM and in 4 cases by using both RB1 and CSP12. There was significant correlation between the ATM and the hemoglobin level of the patients. In addition, the elevated probability of gaining bulky lymphadenopathy was found in ATM positive patients. It is concluded that the I-FISH is a more rapid and sensitive technique for analysis of chromosome aberrations in CLL. A large series study with long-term follow-up is needed to reveal the role of cytogenetic abnormalities in the determination of CLL prognosis.

Curcumin is an excellent lead compound with a variety of bioactivity. Recent articles reported that curcumin's instability and low bioavailability in vivo are mainly due to its easily decomposable beta-diketone moiety. With the aim of bioactive curcumin analogs with better pharmacokinetic property, we present here 11 bis(arylmethenyl)cyclopentanones similar to curcumin and without beta-diketone moiety by reacting relevant arylaldehydes and cyclopentanones. The analogs were structurally determined by 1HNMR and MS spectra, and the crystal structure of 6 was analyzed by X-ray diffraction. Their antibacterial activities in vitro against seven Gram-positive and Gram-negative bacteria were tested, and their inhibition of TNF-alpha and IL-6 secretion in LPS-induced mouse macrophages was investigated using enzyme-linked immunosorbent assay. It was observed that several derivatives displayed higher activity when compared with curcumin, and most of the analogs exhibited activities against the ampicillin-resistant Gram-negative Enterobacter cloacae.

Aim: To study the antitumor effect of IL-23 in mouse mammary cancer and the change of its immune function., Methods: IL-23/MA-891, LXSN/MA-891 and the parental MA-891 cells were inoculated in the subcutaneous tissues of mice, respectively. The mouse models were used to observe the tumorigenic activity of IL-23/MA-891 cells. On the thirtieth day, the spleens and tumors of the mice in three groups were extracted and then IFN-gamma, TNF-alpha, IL-12 and IL-4 were detected by ELISA. The expression of MHC-I, MHC-II, CD80 and CD86 in tumor cells, the ratio of positive cells of CD11c, and the selection of CD4 and CD8 in the spleens were detected by flow cytometry, respectively. CD4 and CD8 in three groups were immuno-stained and then they were examined by microscope., Results: The tumor in the mouse inoculated with IL-23/MA891 cells developed much more slowly than that in the other two groups. Meanwhile, the spleen cells of this group secreted higher IFN-gamma, TNF-alpha and IL-12 than the other two groups (P<0.01), but the secretion of IL-4 in the three groups had no difference (P>0.05). In IL-23/MA891 group, CD4+, CD8+ lymphocytes, CD11c+ cells in spleens and infiltration of CD4+, CD8+ lymphocytes in tumor tissues were also markedly higher than those in LXSN/MA-891 and MA-891 groups (P<0.01). The expression of MHC-I, MHC-II, CD80 and CD86 in IL-23/MA-891 groups was also higher than that in the other two groups (P<0.01)., Conclusion: In the mice the antitumor effect of the mammary cancer cells transferred by IL-23 gene is obvious, which can enhance the cellular immune function and play an important role in inhibiting the growth of tumor.

Background & Objective: Cytokine-based biotherapy is a hot spot in tumor research. This study was to explore the inhibitory effect of interleukin-27 (IL-27) on tumor formation activity of human esophageal carcinoma cell line Eca109 in nude mice, and investigate its antitumor mechanisms., Methods: IL-27 gene was transfected into Eca109 cells with retrovirus vector and stable clones were selected by G418. The expression of IL-27 gene was detected by reverse transcription-polymerase chain reaction (RT-PCR). The secretion of IL-27 from Eca109/IL-27 cells and interferon-gamma (IFN-gamma) in peripheral blood mononuclear cells (PBMCs) were detected by ELISA. Cell proliferation in vitro was assessed by MTT assay. Eca109/IL-27, Eca109/LXSN and Eca109 cells were subcutaneously injected into nude mice to observe the growth of transplanted tumors. The expression of CD16 and FasL in tumor-infiltrating lymphocytes (TIL) and the expression of Fas in tumor cells were detected by flow cytometry., Results: IL-27p28 and IL-27EBI3 were expressed in Eca109/IL-27 cells, but not in Eca109/LXSN and Eca109 cells (P<0.01). IL-27 secretion was significantly higher in Eca109/IL-27 cells than in Eca109/LXSN and Eca109 cells (P<0.01). The proliferation rates of the 3 cell lines were similar (P> 0.05). IFN-gamma secretion was significantly higher in Eca109/IL-27 cell-stimulated PBMCs than in Eca109/LXSN cell-and Eca109 cell-stimulated PBMCs [(56.28+/-1.61) pg/mL vs. (12.70+/-0.82) pg/mL and (11.06+/-0.64) pg/mL, P<0.01]. As compared with those in Eca109 and Eca109/LXSN groups, the tumor growth in nude mice was significantly slower in Eca109/IL-27 group (P<0.05), the expression of CD16 and FasL in TIL and the expression of Fas in tumor cells were up-regulated in Eca109/IL-27 group (P<0.05)., Conclusion: IL-27 gene may inhibit the tumor formation activity of Eca109 cells in nude mouse by activating natural killer (NK) cells through Fas/FasL pathway.

An open label study was conducted in the department of neurosurgery, Beijing Tiantan Hospital in China to determine the incidence of postoperative infections following the use of one or two doses of ceftriaxone administered perioperatively. A total of 343 patients, who required neurosurgery and had satisfied the inclusion criteria, was recruited during a 12 month study period. Of these 343 patients, there were 97 and 107 cases of malignant and benign tumours, respectively, 52 cases of aneurysm, 34 cases of arteriovenous malformation, and 53 other cases who underwent neurosurgery for drainage of sub-dural haematoma, relief of cerebral oedema and other indications. A total of 6 (1.75%) cases of postoperative infection was observed, of which 4 were found in the malignant tumour group, and 2 in the arteriovenous malformation group. All six patients were suffering from meningitis. During the 12 month period immediately prior to the present study, when postoperative penicillin and gentamicin was administered twice daily for 5-7 days as regular prophylaxis against infection, the incidence of postoperative infection was 7.2% in the same department managed by the same staff. Results of our present study suggest that one to two doses of ceftriaxone administered perioperatively are effective in reducing the rate of postoperative infections.