Construction of Ge-Stereogenic Center by Desymmetric Carbene Insertion of Dihydrogermanes.

We developed a method for the enantioselective synthesis of germanium-stereogenic compounds by the desymmetric carbene insertion of dihydrogermanes. A chiral rhodium phosphate catalyst decomposes diaryldiazo-methanes to generate rhodium carbenes that insert enantioselectively into one of the two Ge-H bonds of dihydrogermanes to form germanium-stereogenic compounds under mild reaction conditions. By this method, a variety of chiral germanes with germanium-stereogenic centers were synthesized in high yields and excellent enantioselectivities. Kinetic studies of the reaction showed that the diazo decomposition process was the rate-determining step. The remaining Ge-H bond of the chiral germane products provides a possibility for preparing chiral tetra-substituted germanium-stereogenic compounds.

Role of inhibiting lncRNA TUG1 to down⁃regulate nucleotide binding oligomerization domain like receptor protein 1 inflammasome in delaying the progression of Alzheimer’s disease / 解剖学报

Objective To investigate the relieving effects of knockdown of long non-coding RNA(lncRNA)taurine up-regulated gene 1 (TUG1) on inhibiting nucleotide binding oligomerization domain like receptor protein 1 (NLRP1) inflammasome and the progression of Alzheimer’ s disease. Methods Wild-type (WT group, 10 mice) or amyloid precursor protein (APP) / presenilin-1 (PS1) transgenic mice (30 mice) with a genetic background of C57 / BL6 aged 9-10 weeks were used in this study. APP / PS1 transgenic mice were randomly divided into model group, model+lncRNA TUG1 short hairpin RNA (shRNA) group and model + shRNA non target (NT) group (n = 10) . Blood samples, cerebral cortex tissues, primary microglial cells and primary astrocytes were collected from mice 12 weeks of age on day 1 (3-month-old) and 32 weeks of age on day 1 (8-month-old), with 5 mice per group at each time point. Real-time PCR analysis was used to detect the expression levels of lncRNA TUG1 and macrophage migration inhibitory factor (MIF) mRNA in cerebral cortex tissues and primary microglial cells, and C1r and C1s mRNA levels in primary astrocytes of 3-month-old and 8-month-old mice in the above 4 groups, respectively. ELISA was used to determine the MIF in plasma samples of the above 4 groups of mice. Primary microglia and astrocytes from the cerebral cortex of 3-month-old and 8-month-old mice were co-cultured. CCK-8 method was used to determine the proliferation ability of the above cells. Western blotting was used to determine the expression levels of MIF, pro interleukin-1β (pro-IL-1β), apoptosis associated speck-like protein containing a caspase recrult domain(ASC), Caspase-1 (p20), Caspase-1 (full), NLRP1 and NLRP3 in cerebral cortex tissues of 3-month-old and 8-month-old mice. Immunofluorescent staining was used to determine amyloid beta(Aβ) in cerebral cortex of 8-month-old mice. Results At the age of 3-month-old and 8-month-old, compared with the WT group, the relative expression level of lncRNA TUG1 and MIF in cerebral cortex tissues and primary microglia of model group mice was significantly up-regulated, with primary microglial cells and astrocytes proliferation ability enhanced (P0. 05) . There was no significant difference between the model group and the model+shRNA NT group mice of all the above factors (P>0. 05) . Conclusion In APP / PS1 transgenic mice, up-regulation of lncRNA TUG1 and MIF are positively associated with the activation of NLRP1 inflammasome in mice cerebral cortex tissues and primary microglia. Knock-down of lncRNA TUG1 can ameliorate the progression of Alzheimer’ s disease.

A Spiro Phosphamide Catalyzed Enantioselective Proton Transfer of Ylides in a Free Carbene Insertion into N-H Bonds.

Free carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high-pKa Brønsted acid catalysts that enable free carbene insertion into N-H bonds of amines to prepare chiral α-amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high-energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high-pKa Brønsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products. Computational and kinetic studies uncover the principle for the rational design of proton-transfer catalysts and explain how the catalysts accelerate this transformation and provide stereocontrol.

Platelet-rich plasma protects human keratinocytes from UVB-induced apoptosis by attenuating inflammatory responses and endoplasmic reticulum stress.

BACKGROUND: Although the role of platelet-rich plasma (PRP) in ultraviolet light B (UVB)-induced photoaging has been confirmed in many studies, the specific mechanism is still not clear. Therefore, we attempted to investigate the effect and mechanism of PRP on UVB-induced human keratinocyte (HaCaT cells) apoptosis. METHODS: HaCaT cells were collected to construct UVB-induced photoaging models. Then, the cells were divided into Sham group, 5% PRP group, UVB group, and UVB + 5% PRP group. Next, MTT assay was used to detect the level of cell proliferation; flow cytometry to check the level of apoptosis; ELISA to determine the TNF-α, IL-18, IL-6, and IL-1ß levels in the supernatant; and Western blot to test Bax, Bcl-2, cytochrome c (Cyt.c), GRP78, CHOP, and ATF4 protein expression levels. RESULTS: Briefly, 5% PRP intervention could relieve the inhibition of UVB on HaCaT cell proliferation, inhibit the promotion of UVB to cell apoptosis, up-regulate UVB-induced Bcl-2 protein expression, and decrease Bax and Cyt.c protein level. In addition, 5% PRP significantly down-regulated the inflammatory factor levels of TNF-α, IL-18, IL-6, and IL-1ßin UVB-induced cells and reduced the inflammatory response. Moreover, 5% PRP also greatly reduced the protein expression levels of GRP78, CHOP, and ATF4 in UVB-induced cells and alleviated endoplasmic reticulum (ER) stress. CONCLUSION: PRP may protect HaCaT cells from UVB-induced apoptosis by alleviating inflammatory response and ER stress.

Autologous Platelet-Rich Plasma Repairs Burn Wound and Reduces Burn Pain in Rats.

To investigate the effects of autologous platelet-rich plasma (PRP) on burn wound and burn pain in rats. Rats were treated with high-temperature copper rod to induce skin burn. During treatment, the wound area of rats was recorded on days 0, 3, 7, 10, 14 and healing rates were calculated. After 14-day treatment, the paw withdrawal mechanical threshold (PWMT) as well as paw withdrawal thermal latency were measured. In addition, CD31 expression in burn wound was detected by immunohistochemistry. The contents of TNF-α and IL-1ß in wound tissues were detected by ELISA. Moreover, the mRNA and protein expression levels of VEGF, MMP-9, and TGF-ß1 in wound tissues were detected by RT-qPCR together with Western blot. Burn wound of rats in the PRP group gradually got better with a decreased wound area. Compared with the NS group, the wound area of the PRP group was significantly reduced and the healing rate was significantly increased. Meanwhile, PWMT of the rats in the PRP group was obviously increased compared with the NS group. Compared with the NS group, the rate of CD31-positive cells in the wound tissue of burned rats was increased; while the contents of TNF-α and IL-1ß were significantly decreased after a subcutaneous injection of PRP. In addition, the mRNA and protein expression levels of VEGF, MMP-9, and TGF-ß1 in the wound tissue of rats from PRP group were evidently increased. Autologous platelet-rich plasma not only shortened the healing time, but also relieved the burn pain.

Characterization of Plasmodium berghei Homologues of T-cell Immunomodulatory Protein as a New Potential Candidate for Protecting against Experimental Cerebral Malaria

The pathogenesis of cerebral malaria is biologically complex and involves multi-factorial mechanisms such as microvascular congestion, immunopathology by the pro-inflammatory cytokine and endothelial dysfunction. Recent data have suggested that a pleiotropic T-cell immunomodulatory protein (TIP) could effectively mediate inflammatory cytokines of mammalian immune response against acute graft-versus-host disease in animal models. In this study, we identified a conserved homologue of TIP in Plasmodium berghei (PbTIP) as a membrane protein in Plasmodium asexual stage. Compared with PBS control group, the pathology of experimental cerebral malaria (ECM) in rPbTIP intravenous injection (i.v.) group was alleviated by the downregulation of pro-inflammatory responses, and rPbTIP i.v. group elicited an expansion of regulatory T-cell response. Therefore, rPbTIP i.v. group displayed less severe brain pathology and feverish mice in rPbTIP i.v. group died from ECM. This study suggested that PbTIP may be a novel promising target to alleviate the severity of ECM.

[Preparation of ß-In2S3 and Catalytic Degradation of Oxytetracycline Under Solar Light Irradiation].

The preparation of beta-In2S3 nanomaterial was carried out by reacting In (NO3)3 with thioacetamide through hydrothermal process at 120 degrees C for 12 h. The size and morphology of In2S3 were characterized by the scanning electron microscope (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) while the degradation efficiency was evaluated by the photocatalytic degradation of oxytetracycline under natural sunlight. The results revealed that beta-In2S3 nanoparticles are made up of nanosheets with a length of 15-30 nm and with high efficient catalytic performance, in which more than 98% of the initial oxytetracycline (30 mg x L(-1)) was degraded in 4 h. Furthermore, the prepared pG-In2 S3 can be recycled and kept efficient catalytic performance above 85% even after reusing for four times, which reflected the good stability and relative photocatalytic activity of In2S3.

The alteration of inflammatory markers and apoptosis on chronic prostatitis induced by estrogen and androgen.

PURPOSE: The age-related decline of the testosterone-to-estrogen (T-to-E2) ratio in serum is associated with the increased prevalence of prostatic inflammation. The goal of the study was to induce prostatic inflammation with E2 and androgen treatment and to explore the inflammatory markers and apoptosis on prostatitis. METHODS: Castrated SD rats were treated with E2 and different doses of androgens to achieve an elevated concentration of E2 and a wide range of the androgen-to-E2 ratio in serum. Inflammatory markers TNF-α, COX-2 and MIP-1α were immunohistochemically stained. Apoptosis detection was evaluated by TUNEL staining. E2, T and DHT concentrations in serum were measured, and the relative weight of the prostate and seminal vesicles were determined. RESULTS: T was anti-inflammatory at the doses which normalized or over stimulated the growth of the prostate and seminal vesicles. Experimentally, prostatitis induced by E2 alone increased the prostatic levels of the inflammatory markers TNF-a, COX-2 and MIP-1a. As signs of anti-estrogenic actions, androgens dose-dependently decreased the expression of TNF-α, COX-2 and MIP-1α. Prostatitis induced by E2 alone caused extensive apoptosis in the castrate-resistant cells and E2-induced apoptosis occurred dependently of T manipulation. CONCLUSIONS: Estrogen-alone-induced inflammatory response could promote the expression of inflammatory markers; however, T supplementation reduces the expression of inflammatory markers and E2-induced apoptosis occurs dependently on T manipulation in prostatitis.

Brucella outer membrane protein Omp25 induces microglial cells in vitro to secrete inflammatory cytokines and inhibit apoptosis.

Omp25 protein, an outer membrane protein of Brucella, can cause damage to the central nervous system. As one type of macrophage, microglial cells play a role in immune surveillance and immune protection in the central nervous system; therefore, they are major targets of bacterial attack. The present study examined BV2 mouse microglial cells that were stimulated with different concentrations of Omp25 recombinant protein, and the secretion of inflammatory cytokines by the BV2 cells as well as their level of apoptosis were observed. The objective of the study was to preliminarily illustrate the possible mechanism that Omp25 uses to damage the central nervous system. Mouse BV2 microglial cells were incubated with different concentrations of Omp25 for 24 h, and an enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of the inflammatory cytokines interleukin (IL)-6, tumour necrosis factor (TNF)-α and HMGB1 (high mobility group box-1 protein); reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of TLR4 (Toll-like receptor 4) mRNA; Annexin V-fluorescein isothiocyanate (FITC) double staining was used to detect apoptosis in the BV2 cells. After the BV2 cells were stimulated with different concentrations of Omp25, the levels of IL-6, TNF-α and HMGB1 was increased, and the difference was statistically significant compared with the control group (P<0.05). The secretion of TNF-α and HMGB1 showed a trend toward an initial increase followed by a decrease. The expression level of TLR4 mRNA was increased. Omp25 protein can inhibit apoptosis in BV2 cells. The outer membrane protein Omp25 of Brucella promotes microglial cells to secrete inflammatory cytokines and inhibit apoptosis. TLR4 may be involved in the immune response of the central nervous system to Brucella infection.

Incidence of pleural effusion in patients with pulmonary embolism / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>No data on the incidence of pleural effusion (PE) in Chinese patients with pulmonary embolism are available to date. The aim of the current study was to investigate the frequency of PE in a Chinese population of patients with pulmonary embolism.</p><p><b>METHODS</b>This was a retrospective observational single-center study. All data of computed tomography pulmonary angiography (CTPA) performed over 6-year period on adult patients with clinically suspected pulmonary embolism were analyzed.</p><p><b>RESULTS</b>From January 2008 until December 2013, PE was identified in 423 of 3141 patients (13.5%) with clinically suspected pulmonary embolism who underwent CTPA. The incidence of PE in patients with pulmonary embolism (19.9%) was significantly higher than in those without embolism (9.4%) (P < 0.001). Majority of PEs in pulmonary embolism patients were small to moderate and were unilateral. The locations of emboli and the numbers of arteries involved, CT pulmonary obstruction index, and parenchymal abnormalities at CT were not associated with the development of PE.</p><p><b>CONCLUSIONS</b>PEs are present in about one fifth of a Chinese population of patients with pulmonary embolism, which are usually small, unilateral, and unsuitable for diagnostic thoracentesis.</p>

Isolation of the molecular species of monogalactosyldiacylglycerols from brown edible seaweed Sargassum horneri and their inhibitory effects on triglyceride accumulation in 3T3-L1 adipocytes.

The chemical composition of monogalactosyldiacylglycerols (MGDGs) from brown alga Sargassum horneri and their inhibitory effects on lipid accumulation were investigated in this study. A total of 10 molecular species of MGDGs were identified using nuclear magnetic resonance, alkaline hydrolysis, gas chromatography-flame ionization detector, and high-performance liquid chromatography-tandem mass spectrometry methods. Individual molecular species of MGDGs, including (2S)-1-O-myristoyl-2-O-palmitoleoyl-3-O-ß-D-galactopyranosyl-sn-glycerol (1), (2S)-1-O-myristoyl-2-O-linoleyl-3-O-ß-D-galactopyranosyl-sn-glycerol (3), (2S)-1-O-palmitoyl-2-O-linolenoyl-3-O-ß-D-galactopyranosyl-sn-glycerol (5), (2S)-1-O-myristoyl-2-O-oleyl-3-O-ß-D-galactopyranosyl-sn-glycerol (7), (2S)-1-O-palmitoyl-2-O-palmitoleoyl-3-O-ß-D-galactopyranosyl-sn-glycerol (8), (2S)-1-O-palmitoyl-2-O-linoleyl-3-O-ß-D-galactopyranosyl-sn-glycerol (9), and (2S)-1-O-palmitoyl-2-O-oleyl-3-O-ß-D-galactopyranosyl-sn-glycerol (10), were then furnished using semi-preparative high-performance liquid chromatography, and their inhibitory effects on triglyceride (TG) accumulation and free fatty acid (FFA) levels in 3T3-L1 adipocytes were evaluated. Compounds 3 and 9 showed inhibitory effects on TG and FFA accumulation, with TG levels of 1.568 ± 0.2808 and 1.701 ± 0.1460 µmol/L and FFA levels of 0.149 ± 0.0258 and 0.198 ± 0.0229 mequiv/L, respectively, which were more effective than other compounds. The primary structure-activity relationship suggested that linoleyl [18:2(ω-6)] in the sn-2 position played an important role on triglyceride accumulation inhibition.

Fabrication of magnetic porous Fe-Mn binary oxide nanowires with superior capability for removal of As(III) from water.

Magnetic porous Fe-Mn binary oxide nanowires were successfully fabricated to efficient removal of As(III) from water. The adsorption capacity of the porous nanowires for As(III) obviously increased with increasing of manganese oxide in the composite, accompanying decrease of the saturation magnetization of the adsorbents. Magnetic porous Fe-Mn binary oxide nanowires with an initial Fe:Mn molar ratio of 1:3 exhibited the highest absorption capacity for As(III) and enable magnetic separation from water. The maximal adsorption capacity value is 171mgg(-1) at pH 7.0. In the initial pH range from 3 to 9, 200µgL(-1) of As(III) could be easily decreased to below 10µgL(-1) by the magnetic porous Fe-Mn binary oxide nanowires (0.05gL(-1)) within 75min, and the corresponding residual As was completely oxidized to less toxic As(V). The coexisting chloride, nitrate and sulfate had no significant effect on arsenic removal, whereas, phosphate and humic acid reduced the removal of As(III) by competing with arsenic species for adsorption sites. The resulting magnetic porous Fe-Mn binary oxide nanowires could be a promising adsorbent for As(III) removal from water.

Chemical profiles and identification of key compound caffeine in marine-derived traditional Chinese medicine Ostreae concha.

To compare the chemical differences between the medicinal and cultured oyster shells, their chemical profiles were investigated. Using the ultra performance liquid chromatography-electron spraying ionization-mass spectrometry (UPLC-ESI-MS), combined with principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA), the discrimination of the chemical characteristics among the medicinal and cultured oyster shells was established. Moreover, the chemometric analysis revealed some potential key compounds. After a large-scale extraction and isolation, one target key compound was unambiguously identified as caffeine based on extensive spectroscopic data analysis (1D and 2D NMR, MS, and UV) and comparison with literature data.

[Effect of polymeric aluminum-iron on EPS and bio-flocculation in A2/O system].

Polymeric aluminum-iron (PAFC) was added at the end of aeration tank to enhance phosphorus removal, so that the phosphorus concentration in the effluent could meet the calss A standard in municipal sewage treatment plant pollutant discharge standard (GB 18918-2002). The characteristics of extracellular polymer substances (EPS) and bio-flocculation for the activated sludge in the A2/O system were analyzed in the experiment. The results showed that, the gross of EPS varied little with the increase in PAFC dosage, while, the ratio of albumen to polysaccharide declined from 3.30 to 2.30. When the PAFC dosage increased, the concentration of Al3+ in EPS increased during the whole anaerobic-anoxic-aerobic cycle. The flocs of activated sludge became larger after PAFC addition, Zeta potential of the effluent dropped significantly from - 15.83 mV to -21.20 mV and sludge yield increased. Therefore, bio-flocculation of the activated sludge in the A2/O system improved when a proper amount of PAFC was added, subsequently improve the water quality of the effluent.

Characteristics of pulmonary inflammation in combined pulmonary fibrosis and emphysema / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The condition of concomitant upper lobe emphysema and lower lobe fibrosis as identified by computer tomography is known as combined pulmonary fibrosis and emphysema (CPFE). CPFE has distinct clinical characteristics compared with emphysema alone (EA) and idiopathic pulmonary fibrosis (IPF) without emphysema. However, the pulmonary inflammation characteristics of CPFE are not well known, and the differences between CPFE and the other two diseases with regards to pulmonary inflammation need to be explored. The pulmonary inflammatory characteristics were investigated in CPFE patients and compared with EA and IPF.</p><p><b>METHODS</b>Fraction exhaled nitric oxide (Fe,NO) and differential cell counts, the concentrations of monokine induced by interferon gamma (MIG/CXCL9), interferon-inducible protein 10 (IP-10/CXCL10), and interferon-inducible T cell alpha chemoattractant (I-TAC/CXCL11) were measured in induced sputum obtained from subjects with CPFE (n = 22), EA (n = 22), IPF (n = 14), and healthy volunteers (HV, n = 12). In addition, immunohistochemistry was used to quantify the expression of nitric oxide synthases in alveolar macrophages in 23 lung tissues from patients and control subjects.</p><p><b>RESULTS</b>The CPFE group had higher alveolar NO than subjects in the EA and HV groups (P = 0.009, P = 0.001, respectively) but not than the IPF group (P > 0.05). Numbers of sputum eosinophils were significantly elevated in CPFE and IPF groups compared with the HV group (P = 0.001, P = 0.008). In contrast, eosinophil counts in EA group did not differ from those in the HV group. Compared with the EA and HV groups, the CPFE group had a lower concentration of I-TAC/CXCL11 in sputum supernatants (P = 0.003, P = 0.004). Immunoreactivity for inducible nitric oxide synthase (iNOS) was higher in the CPFE group than in the EA group (P = 0.018, P = 0.006, respectively).</p><p><b>CONCLUSIONS</b>The pulmonary inflammation of CPFE group is more similar to IPF group, while the distal airway inflammation is more significant in CPFE and IPF groups than in EA group. Lung eosinophil cell infiltration and high NOS expression in alveolar macrophage might participate in this pathogenesis.</p>

Pulmonary capillary hemangiomatosis: a clinicopathologic analysis of 2 cases with review of literature / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features of pulmonary capillary hemangiomatosis (PCH).</p><p><b>METHODS</b>The clinical and pathologic profiles of 2 PCH cases were evaluated. Immunohistochemical study (EnVision method) was performed on fixed tissues. The biologic behavior was analyzed with follow-up data.</p><p><b>RESULTS</b>The main presenting symptom was dyspnea. Chest radiography of the two cases depicted diffuse, ground-glass nodules, accompanied by enlarged central pulmonary arteries. Microscopically, the most distinctive feature was proliferation of capillary channels within pulmonary interstitium and alveolar walls, accompanied by muscularization of arterioles. Immunohistochemical study showed an abundance of mast cells in the lesion, and staining for platelet-derived growth factor receptor-beta (PDGFR-β) localized to vascular smooth muscles surrounding the proliferating capillaries and the mast cells. The index of Ki-67 was less than 1 percent and the p53 was negative.</p><p><b>CONCLUSIONS</b>PCH is a rare vascular proliferative disease of yang patients. Increased number of mast cell and the up-regulation of PDGFR-β may suggest mechanism for PCH. The clinical and radiologic diagnosis of PCH can be very difficult, and the histological examination is regarded as the most reliable means to establish the diagnosis. Pathologists should improve their knowledge on PCH.</p>

Inhibition of the expression of prostate specific antigen by curcumin / 药学学报

<p><b>AIM</b>To study the effect of curcumin on the expression of prostate specific antigen (PSA).</p><p><b>METHODS</b>AXSYM system-chemical luciferase method was used to examine the content of PSA in prostate cancer cell lines, LNCap after treated with different doses of curcumin. pGL3-PSA luciferase expression vector, containing 640 bp DNA of PSA gene 5' promoter region was constructed and transfected into LNCap cell with lipofectin. Through detecting the activity of luciferase, the effect of curcumin on the promoter of PSA was studied. Western blotting was used to detect expression of androgen receptor (AR) in LNCap cell with different concentrations of curcumin.</p><p><b>RESULTS</b>The expression of PSA was inhibited and activity of luciferase was reduced by curcumin. There was also significant difference in AR expression as shown by Western blotting experiment after treatment of different doses of curcumin.</p><p><b>CONCLUSION</b>Through inhibiting AR expression, curcumin reduced the function of PSA promoter and inhibited PSA protein expression.</p>