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Objective: The objective of this study was to analyze and compare the effects of different urate-lowering agents on testicular functions in men with gout in a clinical setting. Methods: In this prospective cohort study (Clinical Trial Registration Number: NCT04213534), a total of 49 male patients aged 18–45 years with gout were enrolled. They were divided into three groups and received treatment with either allopurinol, febuxostat or benzbromarone for a duration of 3 months. Semen parameters, reproductive hormones and biochemical assessments were evaluated at baseline, month 1, and month 3. Results: Overall, 40 individuals (81.6%) completed the follow-up visits. In allopurinol group, there were no significant differences in semen parameters from baseline to month 3. Most of sperm parameters in febuxostat group did not show notable changes, except for a decrease in sperm motility at month 3(33.6%, [22.9–54.3] vs 48.4%, [27.4–67.6], p = 0.033). However, the total motile sperm count did not differ significantly after febuxostat treatment. Surprisingly, administration of benzbromarone resulted in improved sperm concentration (37.19 M/mL, [29.6–69.92] vs 58.5 M/mL, [49.8–116.6], p = 0.001). There were no significant changes observed in sperm DNA integrity and reproductive hormones in the three groups from baseline to month 3. The incidence of adverse events did not differ significantly among the three groups as well. Conclusion: This study is the first to demonstrate that urate-lowering agents, allopurinol and febuxostat, do not have clinically relevant negative effects on sperm quality and reproductive hormones in men with gout, and benzbromarone presents improving sperm concentration. Results provide important preliminary guidance for the development of reproductive health management guidelines for patients RCID with gout. [ABSTRACT FROM AUTHOR]

Metagenomic binning is an essential technique for genome-resolved characterization of uncultured microorganisms in various ecosystems but hampered by the low efficiency of binning tools in adequately recovering metagenome-assembled genomes (MAGs). Here, we introduce BASALT (Binning Across a Series of Assemblies Toolkit) for binning and refinement of short- and long-read sequencing data. BASALT employs multiple binners with multiple thresholds to produce initial bins, then utilizes neural networks to identify core sequences to remove redundant bins and refine non-redundant bins. Using the same assemblies generated from Critical Assessment of Metagenome Interpretation (CAMI) datasets, BASALT produces up to twice as many MAGs as VAMB, DASTool, or metaWRAP. Processing assemblies from a lake sediment dataset, BASALT produces ~30% more MAGs than metaWRAP, including 21 unique class-level prokaryotic lineages. Functional annotations reveal that BASALT can retrieve 47.6% more non-redundant opening-reading frames than metaWRAP. These results highlight the robust handling of metagenomic sequencing data of BASALT.Binning is an essential step in genome-resolved metagenomic analysis in which assembled contigs originating from the same source population are clustered. However it is challenging, especially for low abundance microbial species. Here the authors introduce a toolkit that integrates multiple prominent binning tools and AI for efficient and high-resolution recovery of non-redundant bins from short- and long-read metagenomic sequencing datasets. [ABSTRACT FROM AUTHOR]

(1,3;1,4)-β-d-Glucans are widely distributed in the cell walls of grasses (family Poaceae) and closely related families, as well as some other vascular plants. Additionally, they have been found in other organisms, including fungi, lichens, brown algae, charophycean green algae, and the bacterium Sinorhizobium meliloti. Only three members of the Cellulose Synthase-Like (CSL) genes in the families CSLF, CSLH, and CSLJ are implicated in (1,3;1,4)-β-d-glucan biosynthesis in grasses. Little is known about the enzymes responsible for synthesizing (1,3;1,4)-β-d-glucans outside the grasses. In the present study, we report the presence of (1,3;1,4)-β-d-glucans in the exopolysaccharides of the Gram-positive bacterium Romboutsia ilealis CRIBT. We also report that RiGT2 is the candidate gene of R. ilealis that encodes (1,3;1,4)-β-d-glucan synthase. RiGT2 has conserved glycosyltransferase family 2 (GT2) motifs, including D, D, D, QXXRW, and a C-terminal PilZ domain that resembles the C-terminal domain of bacteria cellulose synthase, BcsA. Using a direct gain-of-function approach, we insert RiGT2 into Saccharomyces cerevisiae, and (1,3;1,4)-β-d-glucans are produced with structures similar to those of the (1,3;1,4)-β-d-glucans of the lichen Cetraria islandica. Phylogenetic analysis reveals that putative (1,3;1,4)-β-d-glucan synthase candidate genes in several other bacterial species support the finding of (1,3;1,4)-β-d-glucans in these species. (1,3;1,4)-β-d-Glucans are widely distributed in many organisms, but little is known about the enzymes responsible for their synthesis outside the grasses. Here, the authors report on the presence of (1,3;1,4)-β-d-glucans in the exopolysaccharides of the Gram-positive bacterium Romboutsia ilealis and identify and characterize the (1,3;1,4)-β-d-glucan synthase RiGT2. [ABSTRACT FROM AUTHOR]

Magnesium hydroxide has been successfully used for alkaline reactive dye wastewater treatment. However, for wider range pH values, magnesium hydroxide slurry has a potential advantage due to its buffer action. Reactive orange in aqueous solution was removed by magnesium hydroxide slurry and non-ionic polyacrylamide (PAM) as coagulant aid. Magnesium hydroxide slurry was prepared, and the morphology and particle size were analyzed. The size of flocs and flocculation time have important influence during coagulation-adsorption experiment. Flocculant index (FI), floc size distribution, zeta potential, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR) were used to study the coagulation performance and floc properties. The effects of Mg(OH)2 dosage, PAM dosage, and different pH values on removal efficiency and settling time were investigated. The results show that charge neutralization, precipitation wrapping, and adsorption bridging are the main coagulation mechanisms. The optimal coagulation conditions were as follows: 200 mg/L magnesium hydroxide slurry was added after 3 s of rapid stirring at a speed of 250 rpm; 4 mg/L PAM was added before 15 s of beginning of slow stirring at 60 rpm; the removal efficiency of reactive orange could reach 91.5%. In the range of pH 5–12, magnesium hydroxide slurry shows very good performance for reactive orange removal and floc sedimentation. [ABSTRACT FROM AUTHOR]

Developing new chemically recyclable polymers is important for a circular plastics economy. Herein, we prepared a class of 1,4-dithian-2-one (DTO) with thioether and thioester functionalities. These sulfur-substituted monomers (DTO) showed excellent reactivity for ring-opening polymerization (turnover frequency (TOF) up to 2.3 × 104h−1), which afforded poly(thioether-thioester)s (P(DTO)s) with high air stability, high crystallinity, and commercial high-density polyethylene-like mechanical property (σB = 29.59 ± 1.08 MPa and εB = 749% ± 36%). Intriguingly, chemical recycling of P(DTO) to monomer could be accomplished with excellent efficiency in dilute solution (1 min) at room temperature or even from a commodity plastic waste mixture under catalyst-free thermal bulk condition (180 °C), thus establishing its circular life cycle. P(Me-DTO) could be applied for selective removal of Hg2+ with >99% removal efficiency. More importantly, Me-DTO could be recovered in high yield after utilization for Hg2+ adsorption. [ABSTRACT FROM AUTHOR]

Studying the genetic diversity of nematode parasite populations is crucial to gaining insight into parasite infection dynamics and informing parasite phylogeography. Anisakiasis is a zoonotic disease caused by the consumption of infectious third-stage larvae (L3) of Anisakis spp. carried by marine fish. In the present study, a total of 206 mitochondrial DNA sequences (cytochrome c oxidase 2, cox2) were used to study the genetic diversity, genetic structure, and historical demography of twelve A. pegreffii populations from Trichiurus japonicas along the coast of mainland China and Taiwan. Two distinct evolutionary lineages of A. pegreffii and no significant genealogical structures corresponding to sampling localities suggested that isolation in the marginal seas shaped their patterns of phylogeographic distribution along the coast of mainland China and Taiwan during glaciation with lower sea levels. Furthermore, pairwise FST values and AMOVA did not indicate any significant genetic differentiation among groups with no relation to the geographic area, which might be attributed to fewer barriers to gene flow as well as large population sizes. The results of the neutrality test, mismatch distribution, and Bayesian skyline plot analyses showed that entire population underwent population expansion during the late Pleistocene. Analysis of the demographic history revealed that A. pegreffii underwent historical lineage diversification and admixture due to secondary contact based on ABC analysis. The present research represents the first definitive population structure and demographic history across sampling locations of A. pegreffii along the coast of mainland China and Taiwan. [ABSTRACT FROM AUTHOR]

Trichiurus nanhaiensis is one of the most important commercial fish species in the South China Sea. This study aimed to investigate the level of genetic variation and population genetic structure of T. nanhaiensis in the South China Sea for the first time, using 281 individuals collected from seven locations along the coast of mainland China, Taiwan, and Hainan Island. A high level of haplotype diversity and low nucleotide diversity were detected in the mitochondrial DNA cyt b gene and nuDNA RYR 3 gene. The overall expected heterozygosity (He = 0.693) among the seven populations ranged from 0.681 to 0.706 in microsatellite DNA data, which revealed high levels of genetic diversity. Significant genetic differentiation was found in Taidong populations in Taiwan, revealing the prevention of gene flow caused by the Kuroshio Current. Two major lineages based on the cyt b gene suggested that the Taiwan Strait acted as a geographic barrier for T. nanhaiensis during the glacier periods in the late Pleistocene. The Bayesian skyline plot also revealed that population demographic expansion of T. nanhaiensis was estimated to have occurred in 0.1 Mya. Our results indicated that all populations of T. nanhaiensis had experienced a recent genetic bottleneck following recent expansion based on ABC analysis. [ABSTRACT FROM AUTHOR]

Reverse electrodialysis (RED) is an emerging membrane-based technology for the production of renewable energy from mixing waters with different salinities. Herein, the impact of the stack configuration on the Ohmic and non-Ohmic resistances as well as the performance of RED were systematically studied by using in situ electrochemical impedance spectroscopy (EIS). Three different parameters (membrane type, number of cell pairs and spacer design) were controlled. The Ohmic and non-Ohmic resistances were evaluated for RED stacks equipped with two types of commercial membranes (Type I and Type II) supplied by Fujifilm Manufacturing Europe B.V: Type I Fuji membranes displayed higher Ohmic and non-Ohmic resistances than Type II membranes, which was mainly attributed to the difference in fixed charge density. The output power of the stack was observed to decrease with the increasing number of cell pairs mainly due to the increase in ionic shortcut currents. With the reduction in spacer thickness from 750 to 200 µm, the permselectivity of membranes in the stack decreased from 0.86 to 0.79 whereas the energy efficiency losses increased from 31% to 49%. Overall, the output of the present study provides a basis for understanding the impact of stack design on internal losses during the scaling-up of RED. [ABSTRACT FROM AUTHOR]

Main conclusion: The RgTyDCs possess typical decarboxylase functional activity in vitro and in vivo and participate in acteoside biosynthesis in R. glutinosa, positively controlling its production via activated acteoside/tyrosine-derived pathways. Acteoside is an important ingredient in Rehmannia glutinosa and an active natural component that contributes to human health. Tyrosine decarboxylase (TyDC) is thought to play an important role in acteoside biosynthesis. Several plant TyDC family genes have been functionally characterized and shown to play roles in some bioactive metabolites’ biosynthesis by mediating the decarboxylation of l-tyrosine and l-dihydroxyphenylalanine (l-DOPA); however, one TyDC (named RgTyDC1) in R. glutinosa has been identified to date, but the family genes that contribute to acteoside biosynthesis remain largely characterized. Here, by in silico and experimental analyses, we isolated and identified three RgTyDCs (RgTyDC2 to RgTyDC4) in this species; these genes’ sequences showed 50.92–82.55% identity, included highly conserved domains with homologues in other plants, classified into two subsets, and encoded proteins that localized to the cytosol. Enzyme kinetic analyses of RgTyDC2 and RgTyDC4 indicated that they both efficiently catalysed l-tyrosine and l-dopa. The overexpression of RgTyDC2 and RgTyDC4 in R. glutinosa, which was associated with enhanced TyDC activity, significantly increased tyramine and dopamine contents, which was positively correlated with improved acteoside production; moreover, the overexpression of RgTyDCs led to upregulated expression of some other genes-related to acteoside biosynthesis. This result suggested that the overexpression of RgTyDCs can positively activate the molecular networks of acteoside pathways, enhancing the accumulation of tyramine and dopamine, and promoting end-product acteoside biosynthesis. Our findings provide an evidence that RgTyDCs play vital molecular roles in acteoside biosynthesis pathways, contributing to the increase in acteoside yield in R. glutinosa. [ABSTRACT FROM AUTHOR]

Aim: The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) algorithm for the management of knee osteoarthritis (OA) is available worldwide from 2014, but in 2019 an update was published. Based on this algorithm, a Working Group (WG), including ESCEO members and Chinese experts, wished to see how the new ESCEO algorithm was perceived by Chinese experts in knee OA and how it was integrated into their clinical practice. Methods: A WG was held between members of the international ESCEO task force and a group of Chinese experts. Results: Non-pharmacological approach should be combined with pharmacological interventions. In step 1, symptomatic slow-acting drugs for osteoarthritis (SYSADOA) are the most important background drugs. Evidence, supported by high-quality research, is available only for crystalline glucosamine sulfate (pCGS) and chondroitin sulfate. Topical NSAIDs could be used as an additional option. In step 2, oral NSAIDs could be useful, but cardiovascular/renal/gastrointestinal profiles of the patients should be considered. Intra-articular hyaluronic acid and corticosteroids are alternative to oral NSAIDs, but the evidence is still limited. If steps 1 and 2 are not sufficient, weak opioids could be used. Overall, the conclusions of the ESCEO algorithm are accepted in China for products available in this country. The WG suggests the importance of economic studies, specifically made in China. Conclusion: This work provides evidence-based advice to establish a treatment algorithm in knee OA, for practical implementation in clinical practice in China. [ABSTRACT FROM AUTHOR]

Waterpipe (aka hookah) tobacco smokers are exposed to toxicants that can lead to oxidative DNA and RNA damage, a precursor to chronic disease formation. This study assessed toxicant exposure and biomarkers of DNA [8-oxo-7, 8-dihydro-2′-deoxyguanosine (8-oxodG)] and RNA [8-oxo-7,8-dihydroguanosine (8-oxoGuo)] oxidative damage during smoking of flavored and non-flavored waterpipe tobacco. Thirty waterpipe smokers completed two counterbalanced 2-h lab waterpipe smoking sessions (flavored vs. non-flavored waterpipe tobacco). Urinary concentrations of 8-oxodG and 8-oxoGuo and expired carbon monoxide (eCO) were measured before and after the smoking sessions. A significant increase in the urinary concentrations of 8-oxodG (from 2.12 ± 0.83 to 2.35 ± 0.91 ng/mg creatinine, p = 0.024) and 8-oxoGuo (from 2.96 ± 0.84 to 3.45 ± 0.76 ng/mg creatinine, p = 0.003) were observed after smoking the non-flavored and flavored waterpipe tobacco, respectively. Our results also showed that the mean ± SD of eCO increased significantly after smoking the flavored (from 1.3 ± 1.1 to 20.3 ± 23.6 ppm, p < 0.001) and non-flavored waterpipe tobacco (from 1.8 ± 1.2 to 24.5 ± 26.1 ppm, p < 0.001). There were no significant differences in the means of 8-oxodG (p = 0.576), 8-oxoGuo (p = 0.108), and eCO (p = 0.170) between the flavored and non-flavored tobacco sessions. Smoking non-flavored and flavored waterpipe tobacco leads to oxidative stress and toxicant exposure. Our findings add to the existing evidence about the adverse effects of waterpipe tobacco smoking (WTS) and the need for strong policies to inform and protect young people from the risks of WTS. [ABSTRACT FROM AUTHOR]

To investigate the clinical pattern, survival rate, causes of death and risk factors in a large cohort of Chinese Han patients with systemic sclerosis (SSc). Inpatients treated from 2002 to 2014 were included in this study. Patients were classified into diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc), and SSc-overlap syndrome groups. Data were analyzed using Chi-squared tests, Kaplan-Meier curves, log-rank tests, and Cox proportional hazards modeling. Among a total of 201 patients, dcSSc (50.2%) was the major subtype, followed by lcSSc (30.3%) and SSc-overlap (19.4%). Interstitial lung disease (ILD, 148/201, 74%) was the most frequent organ involvement. The overall survival rates were 98% and 95% at 5 and 10 years, respectively. The overall standard mortality ratio (SMR) was 2.22. The most common cause of death was ILD combined with infection (8/16, 50%), followed by kidney failure (2/16, 12.5%). On crude analysis, pulmonary hypertension, ILD, cardiac involvements, renal involvements, and digital ischemia were associated with poor prognosis. On multivariate analysis, pericardial effusion (p = 0.000) and digital ischemia (p = 0.016) were independent prognostic factors of death. The mortality rate of patients with SSc is mildly increased in comparison with the general population. ILD is the most common systemic involvement and the principal cause of death in SSc. Pericardial effusion and digital ischemia are independent factors associated with death. [ABSTRACT FROM AUTHOR]

Adductomics is expected to be useful in the characterization of the exposome, which is a new paradigm for studying the sum of environmental causes of diseases. DNA adductomics is emerging as a powerful method for detecting DNA adducts, but reliable assays for its widespread, routine use are currently lacking. We propose a novel integrated strategy for the establishment of a DNA adductomic approach, using liquid chromatography-triple quadrupole tandem mass spectrometry (LC-QqQ-MS/MS), operating in constant neutral loss scan mode, screening for both known and unknown DNA adducts in a single injection. The LC-QqQ-MS/MS was optimized using a representative sample of 23 modified 2′-deoxyribonucleosides reflecting a range of biologically relevant DNA lesions. Six internal standards (ISTDs) were evaluated for their ability to normalize, and hence correct, possible variation in peak intensities arising from matrix effects, and the quantities of DNA injected. The results revealed that, with appropriate ISTDs adjustment, any bias can be dramatically reduced from 370 to 8.4%. Identification of the informative DNA adducts was achieved by triggering fragmentation spectra of target ions. The LC-QqQ-MS/MS method was successfully applied to in vitro and in vivo studies to screen for DNA adducts formed following representative environmental exposures: methyl methanesulfonate (MMS) and five N-nitrosamines. Interestingly, five new DNA adducts, induced by MMS, were discovered using our adductomic approach—an added strength. The proposed integrated strategy provides a path forward for DNA adductomics to become a standard method to discover differences in DNA adduct fingerprints between populations exposed to genotoxins, and facilitate the field of exposomics. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HA) hybridized poly(N-isopropylacrylamide)-co-acrylic acid (PNIPAM-co-AAc) hydrogel on thermoplastic polyurethane (TPU) were successfully prepared via photocatalytic polymerization technique. Low temperature plasma processing of HMDSZ and O plasma were deposition on substrate. The HA/hydrogel were stabilized by HA of which the wettability was modified by calcium nitrate and ammonium phosphate dibasic. The HA gradually increases with the increase of time cycles. The deposition of organic silicone group by the HMDSZ on the TPU substrate is hydrophobic surface. When deposition of O, the water contact angles (WCA) was changed to <10° and surface hydrophilicity. The materials were characterized by OM, SEM, FT-IR, XPS and XRD. The results showed that the NIPAM: AAc (1:1 mol) polymers possess macropores ranging from 2 to 20 μm, and their large numbers of carboxyl groups and hydroxyl groups result in a favorable adsorption capacity for HA. Swelling studies indicated that NIPAM: AAc (1:1 mol) was 446 ± 0.3%. This work provided a promising alternative method for the fabrication of polymer materials with tunable and interconnected pores structures for the HA. [ABSTRACT FROM AUTHOR]

Whether hyperuricemia is an independent risk factor for hypertension in adults is still under debate. To determine the association between serum uric acid and risk of hypertension in the Chinese population, we conducted a prospective study using the 'Kailuan Corporation cohort.' A total of 39,233 adult subjects with available data on serum uric acid were enrolled from 2006 to 2007. Subjects with established hypertension were excluded and were then grouped based on the gender and baseline quartile serum uric acid into F1-4 for women and M1-4 for men with F1 and M1 being the lowest quartiles. Incidence of newly described primary hypertension was reevaluated in 2010-2011. The median (interquantile range) baseline uric acid (UA) was 290 (243-344) μmol/L in men and 230 (194-274) μmol/L in women. During a 4-year follow-up period, 12,844 subjects (31.31 %) were newly diagnosed with hypertension. The incidence of hypertension was 14.36, 16.57, 19.06, and 22.35 % in F1 to F4 and 33.64, 33.97, 36.54, and 40.74 % in M1 to M4, respectively. Multiple logistic regression analysis showed that the odds ratios (ORs) of incident hypertension were 1.17 [95 % confidence interval (CI) 1.00-1.37, P = 0.055], 1.24 (95 % CI 1.06-1.45, P = 0.009), and 1.20 (95 % CI 1.02-1.41, P = 0.027) in F2 to F4 compared to the F1 and 0.98 (95 % CI 0.91-1.05, P = 0.534), 1.05 (95 % CI 0.98-1.13, P = 0.190), and 1.13 (95 % CI 1.05-1.22, P = 0.002) in M2 to M4 compared to the M1. Elevated level of serum uric acid is associated with an increased risk of hypertension in adults. [ABSTRACT FROM AUTHOR]

To evaluate the diagnosis value of antibodies to phosphatidylserine/prothrombin complex (aPS/PT) in patients with antiphospholipid syndrome (APS) and to determine the clinical features of APS patients with avidity of aPS/PT. Serum samples were collected from 108 APS patients. Sixty patients with pregnancy morbidity, 37 patients with thrombosis without a history of autoimmune diseases, and 89 healthy blood donors were included as the control group. The enzyme-linked immunosorbent assay (ELISA) test was performed to detect the concentration of aPS/PT, including IgG/M, IgG, and IgM forms, in the same serum sample. The chi-square (χ2) test was used to examine the difference of frequencies of antibodies in APS patients and patients with other diseases. Spearman correlation analysis was performed to investigate the relationship between aPS/PT and other clinical/laboratory parameters. aPS/PT was detectable in 68 (63.0%) of the 108 APS patients, 12 (13.2%) of the 91 disease control patients and 1 (1.1%) of the healthy controls. It was strongly correlated with the activity of lupus anticoagulant (LA) (OR 15.952, 95% CI 7.132-35.678; P < 0.001). The frequency of aPS/PT was 56.9% in anti-cardiolipid antibody (aCL)-negative, 60.5% anti-β2 glycoprotein I antibody (aβ2GPI)-negative, and 50.0% in both aCL and aβ2GPI negative APS patients. The IgG aPS/PT was significantly associated with arterial and venous thrombosis. The aPS/PT antibody could play an important role in the diagnosis of APS, especially in patients with negative aCL and aβ2GPI. It was positively related to thrombotic events in APS. [ABSTRACT FROM AUTHOR]

Rationale: Gypenosides have been reported to produce neuroprotective effects and increase monoamine neurotransmitter levels in the brain. Objective: Considering that depression is involved in monoamine reduction, this study evaluated the antidepressant-like effects of gypenosides in mice exposed to chronic unpredictable mild stress (CUMS). Methods: The sucrose preference test and forced swimming test were performed after administration of gypenosides (at 25, 50, or 100 mg/kg) for 4 weeks. Hippocampal brain-derived neurotrophic factor (BDNF) and its downstream targets were analyzed by western blot. Additionally, hippocampal neuronal proliferation was measured by immunohistochemistry. Results: Four-week treatment with fluoxetine (20 mg/kg) and gypenosides (at either 50 or 100 mg/kg) increased sucrose preference and decreased the immobility time in mice exposed to CUMS. In addition, gypenosides (at either 50 or 100 mg/kg) also increased BDNF expression and neuronal proliferation in the hippocampus of CUMS animals. Further, we showed that treating CUMS mice with K252a, which is an inhibitor of the BDNF receptor TrkB, blocked the effects of gypenosides (100 mg/kg), including behavioral improvements, neuronal proliferation, and up-regulation of p-TrkB, p-ERK, and p-Akt proteins. Conclusions: This study demonstrates that gypenosides exhibit antidepressant-like effects in mice, which may be mediated by activation of the BDNF-ERK/Akt signaling pathway in the hippocampus. [ABSTRACT FROM AUTHOR]

The sulfur-containing reagents dithizone, 2,3-dimercapto-1-propanol, 2-thenoyltrifluoroacetone, 1,3,4-thiadiazole-2,5-dithiol, and 1-(2-thiazolylazo)-2-naphthol (TAN) were first examined with respect to their stabilizing effect on CdTe nanocrystals. The indicator TAN was found to best passivate the surface of CdTe NCs if added during synthesis of the NCs at 100 °C. These NCs (referred to as NC-1) have an emission that peaks at 430 nm, and a quantum yield (QY) of 25 %. If, however, TAN-capped particles are prepared in presence of an ionic liquid at room temperature, the QY of such nanocrystals (referred to as NC-2) is increased by 80 % and the emission peak is shifted to 460 nm. The NC-1 particles bind Ag(I), Pb(II), Hg(II), Fe(III), Cr(III), and Cu(II) in phosphate buffer of pH 6.5 while NC-2 particles bind Cu(II) only. Binding of metal ions is associated with a drop in fluorescence intensity. In case of NC-1, quenching is observed in the 23.3 nM to 23.3 μM Cu(II) concentration range with detection limit of 0.5 nM. In case of NC-2, quenching occurs in the 233 nM to 233 μM Cu(II) concentration range with detection limit of 5.0 nM. The method was applied to the determination of Cu(II) in spiked biosamples, and recoveries of Cu(II) (at a 233 nM level) in BSA and fetal bovine serum using NC-2 are 95 % and 92 %. This is better than the recoveries from the same media with NC-1 (70 % and 32 %). These findings demonstrate that the NC-2 material is superior in terms of selectivity and stability but inferior in terms of detection limit. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

This study is aimed at comparing the efficacy and safety of loxoprofen sodium hydrogel patch (LX-P) with loxoprofen sodium tablet (LX-T) in patients with knee osteoarthritis (OA). One hundred sixty-nine patients were enrolled in a randomized, controlled, double-blind, double-dummy, multicenter, non-inferiority trial of LX-P. Patients were randomly assigned to either LX-P or LX-T groups for a 4-week treatment. The primary efficacy endpoint was the proportion of patients with an overall improvement of ≥50 %, and the secondary efficacy endpoint was the proportion of patients with an improvement of ≥25 % from baseline in each of the seven main symptoms. The non-inferiority trial was based on a power of 80 % and significance level of 2.5 % with a non-inferiority margin of −10 %. In both intention-to-treat (ITT) and per-protocol (PP) analyses, LX-P was as effective as LX-T in regard to the primary endpoint. In the ITT analysis, the difference between the two groups was 12.6 % [95 % confidence interval, −1.7 to 26.9 %]. No significant differences were found between the two groups in any of the secondary efficacy outcomes. A lower incidence of adverse events was observed in LX-P group; however, the difference was not statistically significant. No serious adverse events were reported in the LX-P group, whereas one case was reported in LX-T group. Based on the present study, topical loxoprofen patch was non-inferior to oral loxoprofen in patients with knee osteoarthritis. [ABSTRACT FROM AUTHOR]

8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) is the most investigated product of oxidatively damaged DNA lesion that has been associated with the development of aging, cancer and some degenerative diseases. Here, we present the first liquid chromatography-tandem mass spectrometry method that enables the simultaneous measurement of its repair products in plasma and saliva, namely 8-oxo-7,8-dihydroguanine (8-oxoGua) and 8-oxodGuo. Using this method, we investigated the underlying transport mechanism of the repair products of oxidatively damaged DNA between cellular compartments and biological matrices. Plasma, saliva and urine samples were collected concurrently from 57 healthy subjects. Various deproteinization methods were evaluated, and the precipitants acetonitrile and sodium hydroxide-methanol were, respectively, selected for plasma and saliva samples due to their effect on recovery efficiencies and chromatography. The mean baseline concentrations of 8-oxoGua and 8-oxodGuo in plasma were demonstrated to be 0.21 and 0.016 ng/mL, respectively, while in saliva they were 0.85 and 0.010 ng/mL, respectively. A relatively high concentration of 8-oxoGua was found in saliva with a concentration factor (CF, concentration ratio of saliva to plasma) of 4 as compared to that of 8-oxodGuo (CF: 0.6), implying that 8-oxoGua in plasma may be actively transported to saliva, whereas 8-oxodGuo was most dependent on a passive diffusion. Good correlations between urine and plasma concentrations were observed for 8-oxoGua and 8-oxodGuo, suggesting that blood was a suitable matrix in addition to urine. Significant correlation between 8-oxoGua and 8-oxodGuo in urine was only observed when the concentrations were not corrected for urinary creatinine, raising the issue of applicability of urinary creatinine to adjust 8-oxoGua concentrations. [ABSTRACT FROM AUTHOR]

CdTe quantum dots capped with thioglycolic acid (TGA) display a strong turn-on fluorescence response if exposed to solutions of cysteine (Cys). In order to exploit this effect, a molecularly imprinted polymer (MIP) for Cys was covalently linked to the QDs via allyl mercaptan. The resulting nanomaterials (QDs, MIP-coated QDs, and nonimprint-coated QDs) were characterized by FTIR and scanning electron microscopy. The adsorption of Cys was studied in phosphate buffer (pH 7.4) with respect to equilibration times (5, 15, and 40 min, respectively), binding constants [2.98, 2.42, and 0.96 (×10 M)], and Langmuir isotherms (R = 0.9995, 0.9999, and 0.9983) in the Cys concentration range between 3.33 μM to 500 μM. The method has a detection limit of 0.85 μM (3σ, blank, for n = 10). The selectivity of the MIP-coated QDs for Cys over 19 other amino acids is similar to that of bare QDs, but MIP-QDs afford better recoveries of Cys from solutions also containing bovine serum albumin (90 %) and fetal bovine serum (97 %), respectively, when compared to the recoveries that are obtained with bare (non-imprinted) QDs (135 % and 120 %). This is probably due to the fact that the outer MIP shell largely reduces protein wrapping, dot aggregation, and matrix inclusion. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

A total sample-preparation and analysis time of 50 min is required for the high-throughput method of hair analysis proposed in this paper. The method is applicable to analysis of drugs commonly used in Asia, and their metabolites-methamphetamine (MA), amphetamine (AMP), methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA), ketamine (K), norketamine (NK), dehydronorketamine (DHNK), 6-acetylmorphine (6-AM), morphine (MOR), and codeine (COD). Cut and weighed hair (10 mg) was incubated for 3 min with methanol-trifluoroacetic acid (TFA) during microwave-assisted extraction (MAE) at 700 W. The incubation solution was evaporated, the residue was reconstituted in deionized water-methanol, 99:1 ( v/ v), and 20 μL was injected on to a core-shell column (50 × 4.6 mm, 2.6 μm particle size) for liquid chromatographic-tandem mass spectrometric (LC-MS-MS) analysis. Gradient elution separation was performed in 8 min at a flow rate of 1 mL min. No signal interfering with any of the analytes was found in fourteen blank hair samples from different sources. The limits of detection and quantification were 0.5 pg mg and 2.0 pg mg, respectively, for MA, AMP, MDMA, MDA, K, NK, and DHNK, and 2.0 pg mg and 5.0 pg mg, respectively, for 6-AM, MOR and COD. The linear range was between the LOQ and 1000 pg mg, and the correlation coefficients were all greater than 0.999. Investigation of matrix effects revealed that all the analytes were suppressed by less than 20 % and the standard deviation (SD) was always less than 7 %. Recovery was always greater than 90 % and the SD for each compound was less than 6 %. Precision and accuracy for each analyte were within 15 %. Eight authentic hair specimens from known drug abusers were successfully analyzed. Compared with traditional overnight incubation methods, the rapid 3-min extraction time achieved similar or greater extraction yields. Sample preparation by MAE was a reliable procedure for extraction of the analytes from hair but substantially simpler and faster than other methods. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its urinary metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), are the most investigated carcinogenic biomarkers of tobacco-specific nitrosamines. Here, we report the development of a sensitive and selective assay based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) to simultaneously measure urinary NNK and NNAL. With the use of isotope internal standards and online solid-phase extraction, urine samples were directly analyzed without prior sample purification. The detection limits of this method were 0.13 and 0.19 pg on column for NNK and NNAL, respectively. Inter- and intra-day imprecision was <10 %. Mean recovery of NNK and NNAL in urine was 99-100 %. This method was applied to measure urinary NNK and NNAL in 101 smokers and 40 nonsmokers to assess tobacco exposure. Urinary nicotine, cotinine, N3-methyladenine (N3-MeA), and N7-methylguanine (N7-MeG) were also measured by isotope-dilution LC-MS/MS methods. The results showed that urinary NNK was not observed in all smokers. Urinary free NNAL (0.10 ± 0.09 ng/mg creatinine) and total NNAL (0.17 ± 0.14 ng/mg creatinine) were detected in all smokers. Urinary concentrations of NNAL were significantly correlated with nicotine, cotinine, N3-MeA, and N7-MeG in smokers ( P < 0.001). This method enables the direct and simultaneous measurement of NNK and NNAL in urine using only 50 μL of urine. This study first demonstrated in human that urinary tobacco-specific nitrosamines metabolite (NNAL) are highly correlated with their resulting methylated DNA lesions in urine, which may help to substantiate an increased cancer risk associated with tobacco smoke exposure. [ABSTRACT FROM AUTHOR]

This study aims to investigate the incidence of hepatitis B virus (HBV) reactivation in inflammatory arthritis (IA) patients with HBV infection using anti-tumor necrosis factor (TNF) agents and evaluate the efficacy of antiviral therapy in reducing the risk of viral reactivation in chronic HBV infection. IA patients using anti-TNF agents from six centers were enrolled. Their HBV infection conditions and ALT and HBV-DNA levels were monitored periodically. Among the six chronic hepatitis B patients, HBV reactivation was found in two patients without antivirus prophylaxis and no viral replication was detected in the other four patients with antivirus prophylaxis. In the 31 inactive carriers, the increase of viral load was detected in 6 of 22 (27.3 %) patients without antiviral prophylaxis, and there was no viral reactivation in the other 9 patients with antiviral prophylaxis. HBV reactivation was not found in the 50 patients with resolved HBV infection. It is suggested that anti-TNF therapy might increase the risk of HBV reactivation in patients with chronic HBV infection, and antiviral prophylaxis could effectively decrease the risk. Anti-TNF agents seem to be safe in patients with resolved HBV infection. [ABSTRACT FROM AUTHOR]

Global analyses of DNA methylation contribute important insights into biology and the wide-ranging role of DNA methylation. We describe the use of online solid-phase extraction and isotope-dilution liquid chromatography/tandem mass spectrometry (LC-MS/MS) for the simultaneous measurement of 5-methyl-2′-deoxycytidine (5-medC) and 2′-deoxycytidine (dC) in DNA. With the incorporation of isotope internal standards and online enrichment techniques, the detection limit of this method was estimated to be as low as 0.065 pg which enables human global DNA methylation detection using only picogram amounts of DNA. This method was applied to assess the optimal amounts of enzymes required for DNA digestion regarding an accurate global DNA methylation determination and completeness of digestion and to determine global methylation in human tumor adjacent lung tissue of 79 lung cancer patients. We further determined methylated ( N7-methylguanine ( N7-meG), O-methylguanine ( O-meG), and N3-methyladenine ( N3-meA)) and oxidized DNA lesions (8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG)) in lung cancer patients by LC-MS/MS. Optimization experiments revealed that dC was liberated from DNA much more readily than 5-medC by nuclease P1 and alkaline phosphatase (AP) in DNA, which could lead to an error in the global DNA methylation measurement following digestion with insufficient enzymes. Nuclease P1 showed more differential activity for 5-medC and dC than AP. Global DNA methylation levels in adenocarcinoma and squamous cell carcinoma patients were similar in the range of 3.16-4.01 %. Global DNA methylation levels were not affected by smoking and gender and were not correlated with N7-meG or 8-oxodG in lung cancer patients. Levels of O-meG and N3-meA were however found to be undetectable in all lung tissue samples. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Since methylation at the N-7 and O positions of guanine and the N-3 position of adenine in DNA are the predominant reaction sites, N -methylguanine ( N -MeG), O -methylguanine ( O -MeG), and N -methyladenine ( N -MeA) have been suggested as good biomarkers for assessing exposure to methylating agents. Here, we report the development of a sensitive and selective assay based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) to simultaneously measure N -MeG, O -MeG, and N -MeA in DNA hydrolysates. With the use of isotope internal standards (N- N -MeG, d - O -MeG, and d - N -MeA) and online solid-phase extraction, DNA hydrolysates can be directly analyzed within 12 min without prior sample purification. The limits of detection were 0.02, 0.002, and 0.01 ng/mL on-column (6.1, 0.6, and 3.4 fmol) for N -MeG, O -MeG, and N -MeA, respectively. Inter- and intraday imprecision (CV) were 3.6-9.6% and 2.7-13.6%, respectively. Mean recoveries were 96-109%. This method was then applied to quantitate the amounts of methylated purines in calf thymus DNA treated with methyl methanesulfonate (MMS). The levels of N -MeG, O -MeG, and N -MeA in calf thymus DNA increase with MMS concentration and incubation time. The ratio of relative yields of N -MeG, O -MeG, and N -MeA in MMS-treated DNA was found to be 1.00:0.0032:0.119, respectively. This LC-MS/MS assay provides the sensitivity and high throughput required to evaluate the extent of methylated lesions in DNA induced by methylating agents. [ABSTRACT FROM AUTHOR]

The mobile incoherent Doppler lidar (MIDL), which was jointly developed by State Key Laboratory of Severe Weather (LaSW) of the Chinese Academy of Meteorological Sciences (CAMS) and Ocean University of China, provided meteorological services during the Olympic sailing events in Qingdao in 2008. In this study, two experiments were performed based on these measurements. First, the capabilities of MIDL detection of sea-surface winds were investigated by comparing its radial velocities with those from a sea buoy. MIDL radial velocity was almost consistent with sea-buoy data; both reflected the changes in wind with time. However, the MIDL data was 0.5 m s lower on average than the sea-buoy data due to differences in detection principle, sample volume, sample interval, spatial and temporal resolution. Second, the wind fields during the Olympic sailing events were calculated using a four-dimensional variation data assimilation (4DVAR) algorithm and were evaluated by comparing them with data from a sea buoy. The results show that the calculations made with the 4DVAR wind retrieval method are able to simulate the fine retrieval of sea-surface wind data-the retrieved wind fields were consistent with those of sea-buoy data. Overall, the correlation coefficient of wind direction was 0.93, and the correlation coefficient of wind speed was 0.70. The distribution of retrieval wind fields was consistent with that of MIDL radial velocity; the root-mean-square error between them had an average of only 1.52 m s. [ABSTRACT FROM AUTHOR]

long-lived and loosely organized squall line moved rapidly across Ürümqi, the capital city of Xinjiang Uygur Autonomous Region of China on 26 June 2005, generating hail and strong winds. The squall line was observed by a dual Doppler radar system in a field experiment conducted in 2004 and 2005 by the Chinese Academy of Meteorological Sciences and the local meteorological bureau in northwestern China. The 3D wind fields within the squall line were retrieved through dual Doppler analyses and a variational Doppler radar analysis system (VDRAS). The formation and structure of the squall line as well as the genesis and evolution of embedded convective cells were investigated. During its life period, the squall line consisted of six storm cells extending about 100 km in length, and produced hail of about 25 mm in diameter and strong surface winds up to 11 m s. Radar observations revealed a broad region of stratiform rain in a meso- β cyclone, with the squall line located to the west of this. Two meso- γ scale vortices were found within the squall line. Compared to typical squall lines in moist regions, such as Guangdong Province and Shanghai, which tend to be around 300–400 km in length, have echo tops of 17–19 km, and produce maximum surface winds of about 25 m s and temperature variations of about 8°C this squall line system had weaker maximum reflectivity (55 dB Z), a lower echo top (13 km) and smaller extension (about 100 km), relatively little stratiform rainfall preceding the convective line, and a similar moving speed and temperature variation at the surface. [ABSTRACT FROM AUTHOR]

To study the clinical effificacy of electroacupuncture (EA) on treating knee osteoarthritis (KOA) of Shen (肾)-Sui (髓) insuffificiency (SSI) syndrome type. A total of 245 patients (279 knees) of KOA-SSI were randomly assigned to two groups by lottery: 141 knees in the treatment group and 138 knees in the control group. The treatment group was managed with EA at the dominant points of Neixiyan (Ex-LE4) and Waixiyan (Ex-LE5) as well as the conjugate points of Xuanzhong (GB39) and Taixi (KI3) for 30 min, once a day, with 15 days as one course; 2 courses were applied with a 5-day interval in between. The control group was treated with intra-articular injection of 2 mL hyaluronic acid into the affected joint every 7 days for 5 times in total. The clinical effects on the patients in different stages were observed, and their symptom scores of knee and contents of cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), prostaglandin E2α (PGE2α) and matrix metalloproteinases-3 (MMP-3), in the knee joint fluid were measured before and after treatment. The study was completed in 235 patients (263 knees); four patients (7 knees) in the treatment group and six patients (9 knees) in the control group dropped out. Comparison of therapeutic effects (excellent and effective rates) between the two groups showed insignificant differences (P>0.05). Symptom scores of knee and contents of cytokines in the knee flfluid after treatment were lowered signifificantly in the patients of stage I–III in both groups (P<0.05 or P<0.01). However, the lowering of the total symptom score of knee in the patients of stage III in the treatment group was more signifificant (P<0.05). EA could effectively alleviate the clinical symptoms in KOA patients of stage III, showing an effect superior to that of hyaluronic acid. EA also shows action in suppressing the secretion of IL-1, IL-6, TNF-α, PGE2α and MMP-3 in the knee flfluid. [ABSTRACT FROM AUTHOR]

In this study, PM2.5 in diluted exhausts of motorcycles are collected and emission characteristics of PM2.5-associated polycyclic aromatic hydrocarbons (PAHs) and mutagenicities are investigated. The measured mutagenicity emission factors with metabolic activation for new fuel injection, used fuel injection, new carburetor and used carburetor motorcycles are 7.77 × 104, 1.18 × 105, 1.32 × 105 and 1.15 × 105 rev/km, respectively. The mutagenicity emission factors with metabolic activation are higher than the corresponding values without metabolic activation. The average PAH emission factors are 12.3, 16.3, 25.5 and 26.5 μg/km for new and used fuel-injection motorcycles, and new and used carburetor-operated motorcycles, respectively. The correlation coefficients between PAHs and mutagenicity emission factors are higher with metabolic activation (0.59) than that without metabolic activation (0.31). [ABSTRACT FROM AUTHOR]

Betel quid chewing has been associated with several human cancers. However, the role of betel quid in carcinogenesis remains uncertain. Piper betle contains high concentrations of safrole (an inducer of DNA oxidative damage). Safrole may be metabolized by hepatic sulfotransferase 1A1 (SULT1A1), or glutathione S-transferases (GSTM1, GSTT1, and GSTP1). Thus, we investigated the association of genetic polymorphisms of SULT1A1, GSTM1, GSTT1, and GSTP1 with DNA oxidative damage among betel quid chewers. A biomarker for oxidative stress, urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) level, was analyzed using isotope-dilution LC–MS/MS in 64 betel quid chewers and 129 non-betel quid chewers. Data on demographics and habits (smoking, alcohol drinking, and betel quid chewing) were obtained from questionnaires. Our results revealed that urinary 8-OHdG level was higher in chewers with SULT1A1 Arg-His genotype than in chewers with SULT1A1 Arg-Arg genotype. Urinary 8-OHdG level was also higher in chewers with GSTP1 Ile-Ile genotype. Furthermore, the combined effect of SULT1A1 and GSTP1 genotypes on urinary 8-OHdG was evaluated. Non-chewers with both SULT1A1 Arg-Arg and GSTP1 Val-Val/Ile-Val (reference group) had the lowest mean level (3.6 ng/mg creatinine), whereas chewers with either SULT1A1 Arg-His or GSTP1 Ile-Ile had the highest 8-OHdG mean level (6.2 ng/mg creatinine; vs. reference group, P = 0.04). Chewers with both of SULT1A1 Arg-Arg and GSTP1 Val-Val/Ile-Val (4.6 ng/mg creatinine), and non-chewers with either SULT1A1 Arg-His or GSTP1 Ile-Ile (4.7 ng/mg creatinine) had a moderately increased 8-OHdG level. Thus, the susceptible SULT1A1 and GSTP1 genotypes may modulate increased DNA oxidative stress elicited by betel-quid chewing. [ABSTRACT FROM AUTHOR]

The oxidation resistance of Ti–50Al intermetallics is improved bypreoxidation for 1, 4, or 16 hours in high-pressure, pure oxygen(≈3.9 atm) at 900°C. Specimens preoxidized for 1 hr exhibit betteroxidation resistance than others. Prolonged preoxidation time candeteriorate the oxidation resistance and reduce the parabolic-lineartransition time during subsequent cyclic oxidation in 800°C air. Theoxide-mound occurrence is an important factor for evaluating theeffectiveness of the preoxidation treatment in oxygen. The formationmechanism of Z-phase (Ti5Al3O2) in the Al-depleted layer beneath theflat oxide scale and that beneath the oxide mound are also proposed inthis study. [ABSTRACT FROM AUTHOR]

Stress among university faculty has received considerable treatment in research literature in the past decade in higher education, but very little study has been undertaken from a comparative perspective. This paper reports the results of a comparative study in measuring stress among university faculty in China and Japan using a questionnaire survey. It analyzes the relationship between stress and health in different age groups of the faculty and the differences in the nature and structure of the stress between China and Japan. The research suggests that stress of Chinese and Japanese university faculty can be described as ``social-transformation stress'' and ``direction-conflict stress'', respectively. [ABSTRACT FROM AUTHOR]

In this study, the mixtures of ZnO and Ga2O3 powder with addition of LiCl flux were fired, the raw material mixing ratio, doping with Mn2+ and firing atmosphere effects on phosphor characteristics were investigated. When fired at 1200 °C, its phosphor powder emits a broad-band spectrum range between 375 nm to 700 nm, with a peak at 470 nm. The optimal composition of phosphors is about ZnO/Ga2O5=47/53. Manganese-doped ZnGa2O4, fired in air, exhibits two new emission bands with peaks at 506 nm (Mn2+ emission centre) and 666 nm (Mn4+ emission centre). However, if fired under vacuum, the emission spectrum presents only the 506 nm peak with increased intensity. The 666 nm emission peak derived from a little Mn2 oxidized to Mn4+ which substituted Ga3+ to occupy the B sites of the spinel structure. The emission intensity of the 506 nm peak of Zn1-xMnxGa2O4 is strongest when [Mn2+] x=0.006 and decreases markedly as the concentration of Mn2+ exceeds x=0.01. Most of the substitutional Mn2+ doping species in spinel ZnGa2O4 occupy the zinc sites. The luminescent band was associated to the spin-forbidden transition, 4T1(4G)→6A1 (6S). © 1998 Kluwer Academic Publishers [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that the mammalian target of rapamycin (mTOR) signaling pathway has an important role in ketamine-induced, rapid antidepressant effects despite the acute administration of fluoxetine not affecting mTOR phosphorylation in the brain. However, the effects of long-term fluoxetine treatment on mTOR modulation have not been assessed to date. In the present study, we examined whether fluoxetine, a type of commonly used antidepressant agent, alters mTOR signaling following chronic administration in different brain regions, including the frontal cortex, hippocampus, amygdala and hypothalamus. We also investigated whether fluoxetine enhanced synaptic protein levels in these regions via the activation of the mTOR signaling pathway and its downstream regulators, p70S6K and 4E-BP-1. The results indicated that chronic fluoxetine treatment attenuated the chronic, unpredictable, mild stress (CUMS)-induced mTOR phosphorylation reduction in the hippocampus and amygdala of mice but not in the frontal cortex or the hypothalamus. Moreover, the CUMS-decreased PSD-95 and synapsin I levels were reversed by fluoxetine, and these effects were blocked by rapamycin only in the hippocampus. In conclusion, our findings suggest that chronic treatment with fluoxetine can induce synaptic protein expression by activating the mTOR signaling pathway in a region-dependent manner and mainly in the hippocampus. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a destructive connective tissue disease characterized by dysregulation of the immune system and fibrosis in the skin and internal organs. The pathogenesis of SSc is complex and remains to be determined. So far, limited specific disease-modifying treatments are available for the effective control of fibrosis in patients with SSc. Studies from the past few years hint at the importance of immune dysfunctions, including the dysregulation of innate and adaptive immune cells, as well as the aberrant secretion of inflammatory and fibrotic cytokines, in the pathogenesis of SSc fibrosis. In this Review, we summarize the most pertinent findings concerning the involvement of dysregulated immune responses in fibrosis of the skin and lungs in SSc and highlight the current and potential immune-based targets for SSc therapeutics. [ABSTRACT FROM AUTHOR]