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It is clear that lupus autoimmunity is marked by a variety of abnormalities, including those found at a macroscopic scale, cells and tissues, as well as more microenvironmental influences, originating at the individual cell surface through to the nucleus. The convergence of genetic, epigenetic, and perhaps environmental influences all lead to the overt clinical expression of disease, reflected by the presences of autoantibodies and tissue pathology. This review will address several specific areas that fall among the non-genetic factors that contribute to lupus autoimmunity and related syndromes. In particular, we will discuss the importance of understanding various protein post-translational modifications (PTMs), mechanisms that mediate the ability of 'modified self' to trigger autoimmunity, and how these PTMs influence lupus diagnosis. Finally, we will discuss altered pathways of autoantigen presentation that may contribute to the perpetuation of chronic autoimmune disease. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the effect of melatonin during the culture of donor cells and cloned embryos on the in vitro developmental competence and quality of cloned porcine embryos. At concentrations of 10-6 m or 10-8 m, melatonin significantly enhanced the proliferation of porcine fetal fibroblasts (PFFs), and the blastocyst rate was significantly increased in the 10-10 m melatonin-treated donor cell group. Cloned embryo development was also improved in embryo culture medium that was supplemented with 10-9 m or 10-12 m melatonin. When both donor cells and cloned embryos were treated with melatonin, the cleavage rate and total cell number of blastocysts were not significantly affected; however, the blastocyst rate was increased significantly (20.0% versus 11.7%). TUNEL assays showed that combined melatonin treatment reduced the rate of apoptotic nuclei (3.6% versus 6.1%). Gene expression analysis of the apoptosis-related genes BAX, BCL2L1, and p53 showed that the expression of BCL2L1 was significantly elevated 2.7-fold relative to the control group, while the expression of BAX and p53 was significantly decreased by 3.7-fold and 23.2-fold, respectively. In addition, we detected the expression of two melatonin receptors (MT1 and MT2) in PFFs but not in porcine cloned embryos. We conclude that exogenous melatonin enhances the development of porcine cloned embryos and improves embryo quality by inhibiting p53-mediated apoptotic pathway. The proliferation of PFFs may be mediated by receptor binding, but the beneficial effects of melatonin on embryonic development may be receptor-independent, possibly through melatonin's ability to directly scavenge free radicals. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small noncoding RNAs, which participate in many biological processes. The small RNA transcriptome in the migratory locust has been characterized and 50 conserved miRNA families and 185 potential locust-specific miRNA family candidates have been identified using high-throughput sequencing. However, it is unclear whether miRNAs influence a wide variety of locusts' biological processes, such as growth or development. In insects, Dicer1 ribonuclease transforms miRNA precursors into mature miRNAs. Thus, using systemic RNA interference (RNAi) to silence the expression of Dicer1 in the migratory locust, Locusta migratoria, we reduced miRNA contents in the locust and disrupted two types of molt (nymph-nymph, and nymph-adult). The RNAi of LmDicer1 also resulted in a high mortality in L. migratora. Our study revealed that LmDicer1 was essential for miRNA regulation and development of L. migratoria. These results further support our notion that LmDicer1 could serve as an excellent target for developing novel strategies for controlling this important insect pest. [ABSTRACT FROM AUTHOR]

Modifications of both DNA and protein by methylation are key factors in normal T and B cell immune responses as well as in the development of autoimmune disease. For example, the failure to maintain the methylation status of CpG dinucleotides in DNA triggers T cell autoreactivity. Methylated proteins are known targets of autoimmunity, including the symmetrical dimethylarginine residues of SmD1 and SmD3 in SLE. Herein, we demonstrate that altering the metabolism of S-adenosylmethionine (SAM), the major methyl donor for transmethylation reactions, can suppress T cell immunity. A by-product of SAM metabolism, 5′-deoxy-5′-methylthioadenosine (MTA), and an indirect inhibitor of methyltransferases, inhibits T cell responses including T cell activation markers, Th1/Th2 cytokines and TCR-related signaling events. Moreover, treatment of the lupus-prone MRL/lpr mouse with MTA markedly ameliorates splenomegaly, lymphadenopathy, autoantibody titers as well as IgG deposition and cellular infiltration in the kidney. Incubation of cells with SAM, which increases intracellular MTA levels, inhibits both TCR-mediated T cell proliferation and BCR (anti-IgM)-triggered B cell proliferation in a dose-dependent manner. These studies define the central role of MTA and SAM in immune responses and provide a simple approach to altering lymphocyte transmethylation and T cell mediated autoimmune syndromes. [ABSTRACT FROM AUTHOR]

The cytochrome P450 monooxygenase (cytochrome P450) gene superfamily comprises many genes that may be involved in the biotransformations of pesticides and other xenobiotics. To date, very little is known about cytochrome P450 genes in the oriental migratory locust, Locusta migratoria manilensis. In this study, we carried out a genome-wide analysis of cytochrome P450 genes of the locust to identify putative cytochrome P450 genes and characterize their expression responses to insecticide exposures. We identified 15 cytochrome P450-like genes from a locust expressed sequence tag database (LocustDB). Reverse transcription polymerase chain reaction (RT-PCR) analysis showed that most cytochrome P450-like genes displayed different tissue and developmental stage expression patterns. However, most of them were predominantly expressed in the midgut, gastric caeca, fatbodies, and/or hindgut. Biochemical analysis showed that cytochrome P450 was differentially affected by three different insecticides. Deltamethrin caused significant inductions in 12 h at LD30 (dose to kill 30% of the tested individuals) in the nymphs, whereas malathion and carbaryl did not have significant effect on cytochrome P450 enzyme activity. Further RT-PCR analysis showed significant increases of transcriptions of several cytochrome P450 genes in deltamethrin-treated locusts. Thus, the increased cytochrome P450 enzyme activity is likely due to increased transcriptions of multiple cytochrome P450 genes in response to deltamethrin exposure. These results are expected to help us better understand the interactions between insecticides and major detoxification enzymes, and possible changes of the susceptibility to other insecticides in deltamethrin-treated insects at various molecular levels. [ABSTRACT FROM AUTHOR]

We have developed an unprecedented electron-donor-controlled divergent reaction between N -alkylsulfonylated acrylamides and Br-R F , facilitated by an electron donor-acceptor (EDA) complex, for the synthesis of fluorine-containing oxindoles and amides. Key to this divergent transformation is the EDA complex generation by altering electron donors. This approach has several advantages, such as broad substrate scope, being metal-catalyst- and photocatalyst-free, and having good functional group tolerance.

A photocatalyst-free and EDA complex-enabled radical cascade cyclization reaction of inactive alkenes with bromodifluoroacetamides was reported for the divergent synthesis of fluorine-containing tetralones and quinazolinones. In this transformation, persulfates as electron donors and difluoro bromamide as electron acceptors generate the EDA complex. This is a promising photochemical method with advantages such as mild reaction conditions, simple operation, being metal-free, and excellent functional group tolerance.

With Tongxin, Xiji, and Longde counties in the mountainous area of southern Ningxia as the research area, we used extended-exergy analysis (EEA) to compare their ecological efficiency driving mechanism in 2008-2017 to explore the causes of their variation in ecological degradation. The results showed that the overall difference of ecological efficiency in the three counties was significant during the study period. The ecological efficiency of Tongxin was low, with large inter-annual variation. The ecological efficiency of Xiji was stable, and the overall efficiency of Longde was the highest. The difference of exergy scale was small among the three counties. The exergy proportion in the economic sectors was not coordinated, which were dominated by agricultural and residential sectors. The economic sectors presented significant capital-pull-type and labor-intensive characteristics, indicating the driving force for ecological degradation mainly came from agricultural production and residents' lives in underdeveloped regions. The system's internal exergy conversion rate and the external energy exchange rate of the three counties were extremely low, constituting a simple network circulation path with high input, low storage, low opening and low conversion, which weakened the endogenous development of social economic subsystem and threatened the fragile ecosystem.

Livelihood capital has a close relationship with the income and expenditure of farmers' households. For example, the survival strategies of farmers' households are determined by it and it also influences regional development mechanisms and models. Under the analysis framework of sustainable livelihoods, this study evaluated farmers' livelihood capital, income, and expenditure, based on a participatory rural appraisal and a statistical method, in the development-restricted ecological district of Ningxia, decomposed into the nationality, terrain, and type of farmers' household. Further, by using an index of non-farm business households, the correlations between the livelihood capital and income with the expenditure of farmers' households and the index of non-farm business households were quantified to understand the mechanism of regional development. The results showed that livelihood capital was generally low in the study area. In particular, the livelihood capital of Hui nationality households was slightly higher than that of Han nationality households, that of river valley households was higher than that of mountain households, and that of combined occupation households and non-farm business households was significantly higher than that of agricultural households. Moreover, there was a significant positive correlation between the net annual income of farmers' households and the non-agricultural index, human capital, physical capital, and financial capital, while a significant negative correlation existed between net annual income and natural capital. These findings suggested that efforts were required to enhance the capacity of the non-agricultural index and the human, material, and other capital in the study area. They also served as a guideline for the circulation of peasants' means of production in order to accelerate the polarization of natural capital.

Using Ce, La, Nd (III) nitrate and a curcumin aniline schiff base and a curcumin bis (4-methyl aniline) schiff base as raw materials, six complexes were synthesized. Through the molar conductance, IR, TG-DTA and element analysis motheds, the structures of complexes were characterized. Moreover, the properties of UV-Visible spectra and photochromic properties of the complex, and the solvatechromic performance in organic solvents were explored. The experiments showed that the complexes have good photochromic and solvate-chromic properties. The fluorescence intensity and UV-Visible spectra intensity were reduced under exposure,and the color of the complex solution became light. The complexes have different UV-Visible spectra in difference organic solvents. The relationship between photochromic properties and time was also studied.

Objective: To explore the effect of oxymatrine (OMT) on JAK2/STAT3 signaling in renal tissues of rats with septic shock., Method: The cecal ligation and puncture (CLP) was adopted to establish the rat septic shock model. Fifty-six male SD rats were randomly divided into 7 groups: the sham operation group, the model (CLP) group, CLP + OMT high, middle, low-dose (52, 26, 13 mg x kg(-1), vena caudalis bolus) groups and the positive control (CLP + dexamethasone, 10 mg x kg(-1)) group. The pathological changes in renal tissues were examined with lightmicroscope. BUN content was determined by urine enzymatic method. Expressions of tumournecrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) mRNA in renal tissues were determined by RT-PCR. Expression of JAK2 and STAT3 in renal tissues determined by Western blot. Changes in tumournecrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) contents in renal tissue were determined by radioimmunoassay., Result: OMT of different doses could inhibit the JAK2 and STAT3 activation in renal tissues (P<0.05), and decrease the protein expression of JAK2, STAT3, TNF-alpha and IL-1beta mRNA (P<0.05). Besides, it could reduce TNF-alpha and IL-1beta contents in renal tissue homogenate (P<0.05), serum BUN content (P<0.05), and improve such lesions as tissue hyperemia, edema and inflammatory cell infiltration, with identical results in medium and high-dose OMT groups, and the positive control group., Conclusion: OMT can inhibit JAK2/STAT3 signaling activity to reduce the expression of proin-flammatory factors (TNF-alpha, IL-1beta) and treat the renal injury in rats with septic shock.

Objective: To investigate the clinical features of 3 cases of Burkholderia pseudomallei septicemia in Guangxi Province, and therefore to improve its diagnosis and treatment., Method: The clinical features, treatment and prognosis of 3 cases of acute septicemic melioidosis admitted to this hospital from October 2006 to December 2008 were retrospectively analyzed., Results: The 3 male patients were local farmers, with an average age of (42 ± 2) years. Two of them had a history of frequent trauma and contact with polluted water, and another had a history of exposure to the dust and soil. All patients had an acute onset, manifested as septicemia with chills, high-grade fever, anemia and weight loss. At the same time, the disease was often complicated with multiple organ abscesses. The pus was characterized by smelling like mud. One case was manifestated with lung abscess, with right calf skin pyogenic infection, and the another case was with liver, spleen, pancreas and mediastinal abscess, and the third presented with right facial and ankle soft tissue abscess. The leukocyte counts [(11.6 ± 0.5) × 10(9)/L] and neutrophils [(8.3 ± 0.4) × 10(9)/L] in 2 patients were slightly increased, but decreased in the other patient. There were significant increase of erythrocyte sedimentation rate (63.5 ± 2.7) mm/1 h and c-reactive protein (155 ± 4) mg/L, and liver dysfunction and elevated blood glucose occurred in 3 patients. Chest radiology and CT showed a number of patchy infiltrates, consolidation, and nodules with varying sizes in the upper lung lobes. Abscess in other organs mainly occurred in liver, spleen, and skin. The final diagnosis was confirmed as infection with Burkholderia pseudomallei by repeated blood or pus culture. The isolated Burkholderia pseudomallei was sensitive to carbapenem, and β-lactam + β-lactamase inhibitors. One patient was treated effectively with Imipenem, and other 2 patients with β-lactam + β-lactamase inhibitors. After 3 - 4 days of treatment with antibiotics, the body temperature of these patients gradually decreased, and the intravenous drug was used as long as 4 to 8 weeks, and a total course of antibiotic therapy would continue for 4 to 6 months., Conclusions: Human melioidosis exists in the south and southwest of Guangxi. Repeated blood or pus culture can confirm the diagnosis. A relatively long course of antibiotic treatment with β-lactam/β-lactamase inhibitors or carbapenem is recommended.

Objective: To assess the mean age of sexual activity termination, the prevalence of erectile dysfunction (ED), and their related factors in the old male population in Beijing., Methods: We included in this study 764 males aged over 60 years old received in the health examination clinic and investigated the prevalence of ED and the related factors using the sexual health assessment resource (SHARE) and IIEF-5 questionnaires., Results: The average age of sexual activity termination (no sexual intercourse in over 2 years) was 68.4 +/- 5.2 years among the subjects. The prevalence of ED was 89.4% , of which the rates of mild, moderate and severe ED and non-sexuality were 6.7, 18.6, 28.4 and 35.7% , respectively. Those who had no sexual intercourse for over 2 years because of severe ED accounted for 26.8% among the 60-64 years old males and more than 50% in the >70 yr group. The main risk factors for ED-induced sexual activity termination included age, diabetes, cardiovascular and cerebrovascular diseases, obesity, and low urinary tract symptoms (LUTS)., Conclusion: ED is a common problem as well as the main risk factor for sexual activity termination, and age and general health status are significantly associated with the prevalence of ED among aging males.

Objective: To study the differences in the clinical and laboratory characteristics of disseminated penicilliosis marneffei (PSM) in patients with and without human immunodeficiency virus (HIV) infection., Methods: The clinical data of 33 patients with PSM in our hospital from 2002 to 2007 were retrospectively analyzed. The patients were divided into 2 groups, an HIV infection group (n = 22) and a non-HIV infection group (n = 11). The data of the 2 groups were compared., Results: The common features in the 2 groups included that, the majority of the patients were manual laborers with a low educational level, and the most common clinical characteristics were fever, multiple organ involvement especially the lung, skin, digestive system, and generalized lymphadenopathy. Different characteristics between the 2 groups included, (1) In the non-HIV infection group, the duration of the disease was longer (median: 45 vs 180 d, P < 0.01), with more underlying diseases (5/11) and higher misdiagnosis rate (7/11) as compared to those of the HIV infection group; (2) High, persistent fever, acute dyspnea and molluscum of the skin were more common in the HIV infection group, but intermittent fever, subcutaneous nodules and abscess were the features of the non-HIV infection group. Generalized lymphadenopathy (10/11), bone ache (5/11) and chest pain (7/11) were also more common in the non-HIV infection group (10/22, 2/22, 0/22, respectively in the HIV infection group, P < 0.05; (3) The total white cell counts were mostly increased in the non-HIV infection group (9/11), but were mostly in the normal range (15/22) or decreased (7/22) in the HIV infection group (P = 0.000). The total white cell count, the neutrophil and the lymphocyte counts in the non-HIV infection group were significantly higher than those in the HIV infection group (median: 18.6 x 10(9)/L vs 4.71 x 10(9)/L; 14.24 x 10(9)/L vs 4.16 x 10(9)/L; 2.08 x 10(9)/L vs 0.42 x 10(9)/L, P < 0.01, respectively; (4) The blood CD(4)/CD(8) ratio was normal or higher than 0.5 in the non-HIV infection group, but was, less than 0.5 in the HIV infection group (P = 0.000); (5) The positive rate of blood culture (18/18) or bone marrow culture (14/20) was significantly higher in the HIV infection group than those in the non-HIV infection group (7/10, 2/8, P < 0.05, respectively); (6) Diffuse parenchymal and interstitial changes were the main manifestations of chest radiology in the 2 groups. High-density consolidation and pleuritis were common in the non-HIV infection group, and osteolysis occurred only in the non-HIV infection group (n = 4, P < 0.05); (7) The prognosis was better in the non-HIV infection group (P < 0.05)., Conclusion: Fever, multiple organ dysfunction and poor prognosis are common clinical characteristics of PSM in the 2 groups, but there are significantly different characteristics between the 2 groups in underlying diseases, clinical presentations, disease progress and some laboratory studies.

A fluorescence method is presented for the determination of DNA. The method is based on the interaction of LaL3 [L = morin (2', 3, 4', 5, 7-Pentahydroxyflavone), 2'-OH group deprotonated] with DNA in NH3 x H2O-NH4Cl buffer of pH = 8.0, with lambdaex at 387 nm, and lambdaem at 535 nm. Enhanced fluorescence was observed for LaL3 in the presence of DNA and in the presence of buffer solution of 10%(psi) and ethanol of 10%(psi). The linear range of determination was between 0 and 15 microg x mL(-1) 1 for DNA. The method proved to be simple, easy and sensitive for the determination of DNA. The mechanism of enhancing and the reasons for the effects of acid were also discussed.

Treatment of carcinoma cell lines with 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2), a natural ligand of the peroxisome proliferator-activated receptor-gamma, has been reported to induce apoptosis and/or inhibit proliferation. In this study, we investigated the cytotoxic effect and the action mechanisms of 15d-PGJ2 in a thyroid papillary cancer cell line, CG3. The results indicate that 15d-PGJ2 caused cytotoxicity and increased the amount of intracellular reactive oxygen species (ROS) in these cells. Mitochondrial oxidative phosphorylation inhibitors (carbonyl cyanide m-chloro-phenylhydrazone, oligomycin, cyclosporin A and rotenone), NADPH oxidase inhibitor (diphenyleneiodonium), xanthine oxidase inhibitor (allopurinol) and NO synthase inhibitor (N-monomethyl-L-arginine acetate) did not reduce the generation of ROS. However, catalase, N-acetyl-cysteine and the iron chelator desferri-oxamine decreased the intracellular ROS of 15d-PGJ2-treated CG3 cells. Furthermore, 15d-PGJ2 enhanced the accumulation of iron in the CG3 cells. These data suggest that 15d-PGJ2 induces the generation of ROS by enhancing the accumulation of intracellular iron and that the increased oxidative stress may cause apoptosis of CG3 cells., (Copyright 2002 Lippincott Williams & Wilkins.)

Humic acid (HA), know to be ubiquitous in the natural environment, is present in almost all soil, surface water, and plants. Earlier studies indicate that HA can affect thyroid economy via binding with iodide, inhibiting both thyroid peroxidase and hepatic 5'-deiodinase in rodents. However, the effect of HA, a peroxisome proliferator in rodents, on thyroid hormone receptor (TR) and peroxisome proliferator-activated receptor (PPAR) in human cells has not yet been examined. In this study, we demonstrate that the malic enzyme activity and the transcriptional activities of endogenous TR and PPAR were inhibited after treatment with HA in human hepatocyte Chang liver cell line. Although the protein expression levels of TR-beta, PPAR-alpha and retinoid X receptor-alpha (RXRalpha) were not changed significantly by HA treatment, both the binding abilities of endogenous TR-beta on thyroid hormone response element (TRE) and PPAR-alpha on the PPAR response element (PPRE) were inhibited by HA treatment. The study of the subcellular distribution of HA, relying on the inherent HA fluorescence, showed that HA distributed in the intracellular compartments including cytoplasm and nucleus. The 50% binding inhibition values (CI(50)) of HA on ME-TRE (malic enzyme gene-TRE) and ACOX-PPRE (acylCoA oxidase gene-PPRE) were 19.31 and 19.94 microg/mL, respectively. These results suggest that HA-induced endemic goiter may link in part to the disruption of TRbeta and PPARalpha function in human Chang liver cells. This model may be useful in the investigation of environmental goitrogens.