Migration Inhibition Factor Secreted by Peripheral Blood Memory B Cells Binding to CD74-CD44 Receptor Complex Drives Macrophage Behavior in Alzheimer's Disease.

Dysregulation of the peripheral immune system is be involved in the neuroinflammation in Alzheimer disease (AD) and accelerate the disease progression. The contribution of immune cells, particularly B cells, to AD pathogenesis has gained attention in recent research. In this study, we investigated the role of Peripheral Blood Memory B cells (PBMBs) and their secreted Migration Inhibition Factor (MIF) in driving macrophage behavior in AD based on the scRNA-seq technique, immunofluorescence and flow cytometry. We discovered that MIF binds to the CD74-CD44 receptor complex on macrophages, influencing their behavior. The dysregulated macrophage response hampers the clearance of amyloid-beta (Aß) plaques, exacerbating AD pathology. Targeting the MIF-CD74-CD44 signal pathway may hold therapeutic potential in modulating macrophage activity and mitigating neuroinflammation in AD. This study provides a further understanding of peripheral immune cells dysregulated in AD.

Multi-Omics Analysis of the Effects of Soil Amendment on Rapeseed (Brassica napus L.) Photosynthesis under Drip Irrigation with Brackish Water.

Drip irrigation with brackish water increases the risk of soil salinization while alleviating water shortage in arid areas. In order to alleviate soil salinity stress on crops, polymer soil amendments are increasingly used. But the regulation mechanism of a polymer soil amendment composed of polyacrylamide polyvinyl alcohol, and manganese sulfate (PPM) on rapeseed photosynthesis under drip irrigation with different types of brackish water is still unclear. In this field study, PPM was applied to study the responses of the rapeseed (Brassica napus L.) phenotype, photosynthetic physiology, transcriptomics, and metabolomics at the peak flowering stage under drip irrigation with water containing 6 g·L-1 NaCl (S) and Na2CO3 (A). The results showed that the inhibitory effect of the A treatment on rapeseed photosynthesis was greater than that of the S treatment, which was reflected in the higher Na+ content (73.30%) and lower photosynthetic-fluorescence parameters (6.30-61.54%) and antioxidant enzyme activity (53.13-77.10%) of the A-treated plants. The application of PPM increased the biomass (63.03-75.91%), photosynthetic parameters (10.55-34.06%), chlorophyll fluorescence parameters (33.83-62.52%), leaf pigment content (10.30-187.73%), and antioxidant enzyme activity (28.37-198.57%) under S and A treatments. However, the difference is that under the S treatment, PPM regulated the sulfur metabolism, carbon fixation and carbon metabolism pathways in rapeseed leaves. And it also regulated the photosynthesis-, oxidative phosphorylation-, and TCA cycle-related metabolic pathways in rapeseed leaves under A treatment. This study will provide new insights for the application of polymer materials to tackle the salinity stress on crops caused by drip irrigation with brackish water, and solve the difficulty in brackish water utilization.

G-/C-rich ssDNA-based Fe and Cu/Fe nanoclusters with peroxidase-like activity for intracellular ROS production and cytotoxicity applications.

Five G-/C-rich single-stranded DNA (ssDNA) with different sequences and lengths were templated to prepare the DNA-Cu, DNA-Fe, and bimetallic DNA-Cu/M nanoclusters (NCs). The peroxidase-like activities of these nanomaterials were studied using H2O2 and 3,3',5,5''-tetramethylbenzidine (TMB) as the reaction substrates in HAc-NaAc buffer. It was found that T30-G2-Fe NCs and T30-G2-Cu/Fe NCs, with a size of about 2 nm, exhibit similar and the strongest enzyme-like activity under optimal conditions. Both NCs possess a similarly high affinity to substrates, and the Michaelis-Menten constant (Km) values to TMB and H2O2 are about 11 and 2-3 times lower than those of natural horseradish peroxidase (HRP), respectively. The activity of both nanozymes decreases to about 70% after being kept for one week in pH 4.0 buffer at 4 °C, which is comparable with HRP. Hydroxyl radicals (•OH) are the main reactive oxygen species (ROS) produced in the catalytic reaction. Moreover, both NCs can facilitate in situ generation of ROS in HeLa cells using endogenous H2O2. MTT assays indicate that the T30-G2-Cu/Fe NCs exhibit the strong selective cytotoxicity to HeLa cells over HL-7702 cells. The cellular viability is about 70% and 50% after incubating with 0.6 M NCs for 24 h without or with 2 mM H2O2, respectively. The current study shows that the T30-G2-Cu/Fe NCs have the potential for chemical dynamic treatment (CDT).

A stilbene derivative as dual-channel fluorescent probe for mitochondrial G-quadruplex DNA in living cells.

G-quadruplex DNA has attracted the widespread attention as a novel target of anticancer strategy. Herein, two novel stilbene derivatives 2a and 2b were designed and synthesized under mild reaction conditions, and their interactions with G-quadruplex DNA, cytotoxicity, and distribution in living cells were investigated in detail. Both compounds display a low cytotoxicity and the higher affinity to G-quadruplex DNA than to the other secondary structures, including duplex, single-stranded and i-motif DNA, moreover, the affinity of 2b with m-allyl pyridine salt group to G-quadruplex DNA is about 10-fold stronger than that of 2a with p-allyl pyridine salt group. The interactions of the compounds with the promoter G-quadruplexes are enthalpy-driven by an ITC assay. 2a and 2b not only stabilize the G-quadruplex structure but also induce the G-rich sequences (bcl-2, HRCC and KSS) to fold into the mixed-type G-quadruplex in Na+/K+ free Tris-HCl buffer at pH 7.0, and 2b presents the higher stabilization to G-quadruplex than 2a by a FRET-melting assay. 2b presents a dual-emission at 508 and 600 nm and gives a turn-on and stronger and more sensitive fluorescence response over 2a to the promoter (bcl-2, c-kit 2 and c-myc) and mitochondrial (HRCC and KSS) G-quadruplex DNA at both emission wavelengths, moreover, the peak at 508 nm is blue-shifted to 466 nm after binding to DNA. The blue and red dual-channel CLSM images indicate that 2b is mainly distributed in the mitochondrion of living HepG2 cells. The results show that 2b is a potential dual-channel fluorescent probe for mitochondrial G-quadruplex DNA in living cells.

Single-Cell Sequencing Revealed Pivotal Genes Related to Prognosis of Myocardial Infarction Patients.

Objectives: Myocardial infarction (MI) is a common cardiovascular disease. Histopathology is a main molecular characteristic of MI, but often, differences between various cell subsets have been neglected. Under this premise, MI-related molecular biomarkers were screened using single-cell sequencing. Methods: This work examined immune cell abundance in normal and MI samples from GSE109048 and determined differences in the activated mast cells and activated CD4 memory T cells, resting mast cells. Weighted gene coexpression network analysis (WGCNA) demonstrated that activated CD4 memory T cells were the most closely related to the turquoise module, and 10 hub genes were screened. Single-cell sequencing data (scRNA-seq) of MI were examined. We used t-distributed stochastic neighbor embedding (t-SNE) for cell clustering. Results: We obtained 8 cell subpopulations, each of which had different marker genes. 7 out of the 10 hub genes were detected by single-cell sequencing analysis. The expression quantity and proportion of the 7 genes were different in 8 cell clusters. Conclusion: In general, our study revealed the immune characteristics and determined 7 prognostic markers for MI at the single-cell level, providing a new understanding of the molecular characteristics and mechanism of MI.

Crescent-Shaped Carbazole Derivatives as Light-Up Fluorescence Probes for G-Quadruplex DNA and Live Cell Imaging.

In recent years, studies on the organic small molecule fluorescent probes targeting G-quadruplexes have attracted a wide attention, because G-quadruplexes play an important role in various biological functions. Herein, we reported three crescent-shaped carbazole derivatives (4a-4c) and studied their interactions with the single-stranded, duplex, G-quadruplex and i-motif DNA. Both 4b and 4c have an above 100 nm Stokes shift and low fluorescence intensity, moreover, they exhibit the stronger affinity to G-quadruplex than to the other DNA structures. 4b with a cyanovinyl pyridine salt group displays a specific light-up fluorescence response to G-quadruplexes. FRET and CD results suggest that both 4b and 4c are able to improve the stability of G-quadruplexes and maintain their topology, moreover, they induce G-rich sequences (bcl-2, HTG, and KSS) to fold into G-quadruplexes in Na+ /K+ free buffer. In addition, CLSM images suggest that 4b and 4c are mainly distributed in the mitochondrion of living HepG2 cells, and a weak fluorescence signal is also observed in the nucleus for 4c. Given that the two compounds have the larger association constants to G-quadruplexes over to duplex and single-stranded DNA, we speculate that the fluorescence signals in cells may mainly be attributed to the compound/G-quadruplex DNA complexes.

Highly selective turn-on red fluorescence probes for visualization of the G-quadruplexes DNA in living cells.

Studies on small molecule fluorescent probes for detecting G-quadruplexes DNA have bring about an extensive attention in recent years. In this paper, we designed and synthesized three benzothiazole derivatives named 2a-2c under moderate reaction conditions and investigated their interactions with DNA (single-stranded, duplex, i-motif and G-quadruplex) and distribution in living cell. Three compounds present a large Stokes shift (∼90 nm) and a weak red fluorescence emission, and they exhibit a good selectivity and sensitive turn-on fluorescence response for the promoter G-quadruplex DNA (bcl-2, c-myc and c-kit 2) and mitochondria G-quadruplex (KSS). The affinity of 2a and 2b with N-alkyl side chain group to DNA is stronger than that of 2c with an anion group, therefore, they also increase the stability of the G-quadruplex structure. 2b induces the conformational change of both bcl-2 and KSS G-quadruplexes, while all compounds induce the folding of bcl-2 from the coiled structure to the hybrid G-qrudruplex. Three compounds interact with the G-quadruplex DNA mainly by end-stacking mode. Furthermore, MTT assays and confocal fluorescence images show that these compounds can enter the living HepG2 cells with low cytotoxicity. 2a-2c are mainly located in the mitochondrion and interacted with mitochondria G-quadruplex DNA, while only weak fluorescence can be found in cell nucleus. In a word, 2a-2c can be implied in image of G-quadruplex DNA in living cells.

Weighted correlation network bioinformatics uncovers a key molecular biosignature driving the left-sided heart failure.

BACKGROUND: Left-sided heart failure (HF) is documented as a key prognostic factor in HF. However, the relative molecular mechanisms underlying left-sided HF is unknown. The purpose of this study is to unearth significant modules, pivotal genes and candidate regulatory components governing the progression of left-sided HF by bioinformatical analysis. METHODS: A total of 319 samples in GSE57345 dataset were used for weighted gene correlation network analysis (WGCNA). ClusterProfiler package in R was used to conduct functional enrichment for genes uncovered from the modules of interest. Regulatory networks of genes were built using Cytoscape while Enrichr database was used for identification of transcription factors (TFs). The MCODE plugin was used for identifying hub genes in the modules of interest and their validation was performed based on GSE1869 dataset. RESULTS: A total of six significant modules were identified. Notably, the blue module was confirmed as the most crucially associated with left-sided HF, ischemic heart disease (ISCH) and dilated cardiomyopathy (CMP). Functional enrichment conveyed that genes belonging to this module were mainly those driving the extracellular matrix-associated processes such as extracellular matrix structural constituent and collagen binding. A total of seven transcriptional factors, including Suppressor of Zeste 12 Protein Homolog (SUZ12) and nuclear factor erythroid 2 like 2 (NFE2L2), adrenergic receptor (AR), were identified as possible regulators of coexpression genes identified in the blue module. A total of three key genes (OGN, HTRA1 and MXRA5) were retained after validation of their prognostic value in left-sided HF. The results of functional enrichment confirmed that these key genes were primarily involved in response to transforming growth factor beta and extracellular matrix. CONCLUSION: We uncovered a candidate gene signature correlated with HF, ISCH and CMP in the left ventricle, which may help provide better prognosis and therapeutic decisions and in HF, ISCH and CMP patients.

The sensitive detection of ATP and ADA based on turn-on fluorescent copper/silver nanoclusters.

A simple turn-on fluorescence strategy is proposed for the detection of ATP based on DNA-stabilized copper/silver nanoclusters (DNA-Cu/Ag NCs). The fluorescence intensity of DNA-Cu/Ag NCs increases significantly in the presence of ATP, because the specific interaction between ATP and its aptamer causes two darkish Cu/Ag NCs to be situated at the 5' and 3' termini close to each other. A limit of detection (LOD) of 7.0 µM is found, in a linear range of 2-18 mM, and the proposed sensor is simple, sensitive, and selective. Additionally, the DNA-Cu/Ag NCs/ATP system is further developed into a sensor for ADA detection and demonstrates a linear response to ADA from 5 to 50 U/L with a LOD of 5 U/L. The proposed method is also shown to be successful in detecting ATP and ADA in a solution of fetal bovine serum.

An aptasensor for the label-free detection of thrombin based on turn-on fluorescent DNA-templated Cu/Ag nanoclusters.

A highly sensitive thrombin aptasensor was constructed based on the alteration of the aptamer conformation induced by the target recognition and the turn-on fluorescence due to the proximity of two darkish DNA-templated copper/silver nanoclusters (DNA-Cu/Ag NCs). Two DNA templates were designed as the functional structures consisting of the Cu/Ag NC-nucleation segment located at two termini or one terminus and the aptamer segment in the middle of a DNA template. Two darkish DNA-Cu/Ag NCs came close to each other when the aptamer combined with the target due to the conformational alteration of the aptamer structure, resulting in an increased fluorescence signal readout. Thrombin was sensitively determined as low as 1.6 nM in the range of 1.6-8.0 nM with a high selectivity. Finally, this sensor succeeded in detecting thrombin in a real fetal bovine serum.

Cytosine-rich ssDNA-templated fluorescent silver and copper/silver nanoclusters: optical properties and sensitive detection for mercury(II).

DNA-templated silver nanoclusters (DNA-Ag NCs) with cytosine (C)-rich sequences (four or more segments of consecutive (2-5) C-bases) were synthesized. They display green and/or orange/red emissions under different excitation wavelengths. There is indication that more consecutive C-bases lead to longer emission wavelengths. The ratio of the red and green emissions of the DNA-Ag NCs depends on whether the NCs were synthesized under acidic or basic conditions. We also prepared the DNA copper/silver nanoclusters (DNA-Cu/Ag NCs) which can be synthesized in shorter time and display higher stability. The DNA-Cu/Ag NCs, under 470 nm photoexcitation, always display green emission, with a peak at 550 nm, irrespective of whether being prepared under acidic or basic conditions. The fluorescence of the Cu/Ag NCs is selectively quenched by Hg(II) ions which can be quantified by this nanoprobe with a detection limit as low as 2.4 nM. The quenching mechanism was studied by Stern-Volmer plots and lifetime studies which revealed that both static and dynamic quenching are operative. Graphical abstract Schematic presentation of fluorescent DNA-Ag nanoclusters (NCs) exhibiting red and green emission under different pH values, and green emissive DNA-Cu/Ag NCs for sensitive and rapid detection of Hg2+.

Meta-analysis of related factors of impulse control disorders in patients with Parkinson's disease.

BACKGROUND: To explore the related factors of impulse control disorders (ICDs) in patients with Parkinson's disease (PD). METHODS: We conducted a comprehensive search to identify studies on impulse control disorders in patients with Parkinson's disease. The related factors were compared to discriminate between PD patients with ICDs (PD-ICDs+)and PD patients without ICDs(PD-ICDs-)by a meta-analysis. RESULTS: 96 full-texts were assessed, and 15 were included (PD-ICDs+: 999; PD-ICDs-: 3507). The results showed that PD-ICDs + were significantly associated with younger age (SMD =-0.39, 95% CI: -0.50 - -0.28, P < 0.01), male sex(OR = 1.64, 95% CI: 1.34-2.02, P < 0.01), smoking habit(OR = 2.28, 95% CI: 1.16-4.47,P = 0.02), dopamine receptor agonist use(DA use) (OR = 3.41, 95% CI: 1.86-6.26,P < 0.01), dopamine receptor agonist equivalent daily dose(DA LEDD) (SMD = 0.42, 95% CI: 0.14 - 0.70,P = 0.003), levodopa equivalent daily dose(total LEDD) (SMD = 0.32, 95% CI: 0.14 - 0.49,P < 0.01), and amantadine use(OR = 2.26, 95% CI: 1.67-3.06,P < 0.01). While levodopa dose (SMD = 0.05, 95% CI: -0.09 -0.19,P = 0.48), Hoehn and Yahr stage(H & Y stage) (SMD =-0.05, 95% CI: -0.14 - 0.04,P = 0.27), MDS-UPDRS Part III score(UPDRS III score) (SMD =-0.05, 95% CI: -0.13 - 0.03,P = 0.24), PD duration (SMD =-0.23, 95% CI: 0.10 - 0.37,P < 0.01)and Mini-Mental Status Examination score (MMSE score) (SMD = 0.10, 95% CI: -0.11 - 0.31,P = 0.33)were not related with PD-ICDs+. CONCLUSION: Our study confirmed the previous results that younger age, male gender, smoking habit, longer PD duration, DA use, DA LEDD, total LEDD were high risk factors of PD-ICDs+.

Vaspin Prevents Tumor Necrosis Factor-α-Induced Apoptosis in Cardiomyocytes by Promoting Autophagy.

Visceral adipose tissue-derived serine protease inhibitor (Vaspin) is an adipocytokine that has been shown to exert anti-inflammatory effects and inhibits apoptosis under diabetic conditions. This study was designed to investigate the impact of vaspin on autophagy in tumor necrosis factor (TNF)-α-induced injury in cardiomyocytes and its cardioprotective effects in the pathogenesis of diabetic cardiomyopathy (DCM). H9C2 cells were treated with TNF-α with or without vaspin in vitro. Tumor necrosis factor-α treatment inhibited autophagy and promoted apoptosis in H9C2 cells after stimulating for 24 hours. Pretreatment with vaspin significantly mitigated apoptosis induced by TNF-α partly because of augment effects of vaspin on autophagy as demonstrated by a higher ratio of LC3-II/LC3-I, higher expression of Beclin-1, and increased autophagosomes formation. Furthermore, the AKT agonist IGF-1 significantly reversed the effect of vaspin on autophagy. In vivo DCM model was also developed by treating rats with streptozotocin followed by intraperitoneal injection with vaspin. In DCM rats, upregulation of vaspin reversed cardiac dysfunction, as identified by increased left ventricular ejection fractions and fractional shortening levels, a higher Em/Am ratio, and lower levels of TNF-α, lactate dehydrogenase, creatine kinase, and creatine kinase-myocardial isoenzyme. In conclusion, vaspin attenuated the TNF-α-induced apoptosis by promoting autophagy probably through inhibiting the PI3K/AKT/mTOR pathway and further ameliorated the cardiac dysfunction in DCM rats.

Regulation of TLR4 expression mediates the attenuating effect of erythropoietin on inflammation and myocardial fibrosis in rat heart.

The mechanism underlying the anti­inflammatory or antifibrotic activity of erythropoietin (EPO) in myocardial fibrosis (MF) remains elusive. In the current study, abdominal aortic constriction (AAC) was performed on rats and EPO and/or Toll­like receptor (TLR)4 were overexpressed in rat hearts through intramyocardial administration of lentivirus expressing the EPO and TLR4 genes. Hematoxylin and eosin staining and Masson's trichrome staining were performed on tissue sections from rat hearts for histopathological examination. ELISA was used to determine the levels of inflammatory mediators in serum. Gene expression levels were determined by quantitative polymerase chain reaction analysis and protein expression levels were determined by western blot analysis and immunofluorescence staining. The results indicated that EPO overexpression improved MF in rat hearts, by inhibiting the release of transforming growth factor (TGF)­ß1, tumor necrosis factor (TNF)­α, interleukin (IL)­6, IL­1ß, IL­17A, matrix metalloproteinase (MMP)­9 and MMP­2. Moreover, EPO overexpression suppressed the expression of TLR4, while promoting phosphoinositide 3­kinase (PI3K) and phosphorylated AKT serine/threonine kinase 1 (Akt) expression levels. However, the beneficial effects of EPO were attenuated by overexpression of TLR4. In addition, inhibition of PI3K/Akt signaling activity by treatment with LY294002 markedly reversed the protective effect of EPO on the AAC­induced MF. Taken together, the present study demonstrated that EPO may have a critical role against MF by activating PI3K/Akt signaling and by downregulating TLR4 expression, thereby inhibiting the release of TGF­ß1, TNF­α, IL­6, IL­1ß, IL­17A, MMP­9 and MMP­2. These findings suggest that the PI3K/Akt/TLR4 signaling pathway is associated with the anti­inflammatory effects of EPO and may play a role in attenuating AAC­induced MF.

Highly sensitive and selective detection of Pb2+ using a turn-on fluorescent aptamer DNA silver nanoclusters sensor.

A novel turn-on fluorescent biosensor has been constructed using C-PS2.M-DNA-templated silver nanoclusters (Ag NCs) with an average diameter of about 1 nm. The proposed approach presents a low-toxic, simple, sensitive, and selective detection for Pb2+. The fluorescence intensity of C-PS2.M-DNA-Ag NCs enhances significantly in the presence of Pb2+, which is attributed to the special interaction between Pb2+ and its aptamer DNA PS2.M. Pb2+ induces the aptamer to form G-quadruplex and makes two darkish DNA/Ag NCs located at the 3' and 5' terminus close, resulting in the fluorescence light-up. Moreover, Pb2+ can be detected as low as 3.0 nM within a good linear range from 5 to 50 nM (R = 0.9862). Furthermore, the application for detection of Pb2+ in real water samples further demonstrates the reliability of the sensor. Thus, this sensor system shows a potential application for monitoring Pb2+ in environmental samples.

A molecular beacon based on DNA-templated silver nanoclusters for the highly sensitive and selective multiplexed detection of virulence genes.

In this work, we develop a fluorescent molecular beacon based on the DNA-templated silver nanoclusters (DNA-Ag NCs). The skillfully designed molecular beacon can be conveniently used for detection of diverse virulence genes as long as the corresponding recognition sequences are embedded. Importantly, the constructed detection system allows simultaneous detection of multiple nucleic acids, which is attributed to non-overlapping emission spectra of the as-synthesized silver nanoclusters. Based on the target-induced fluorescence enhancement, three infectious disease-related genes HIV, H1N1, and H5N1 are detected, and the corresponding detection limits are 3.53, 0.12 and 3.95nM, respectively. This design allows specific, versatile and simultaneous detection of diverse targets with easy operation and low cost.

Studies on interactions of carbazole derivatives with DNA, cell image, and cytotoxicity.

DNA-binding agents have been considered as an established opportunity for the development of anticancer drugs and DNA fluorescence probes. This work reported the synthesis of two novel carbazole derivatives (1 and 2) and investigated their DNA binding properties, living cell image, and cytotoxicity. The results demonstrated that both compounds presented the higher binding affinity to G-quadruplex than to duplex DNA by means of UV-Vis absorption titration and fluorescent intercalator displacement. Continuous variation analysis indicated that their binding stoichiometries of the compound/G-quadruplex were near 2 except the compound/bcl-2. Circular dichroism spectra showed that both compounds had no influence on the conformation of G-quadruplexes. Fluorescence titrations indicated that 2 had the potential to be a G-quadruplex selective fluorescent probe, while 1 could be used as a fluorescent probe for duplex DNA. Confocal fluorescence images indicated that both compounds could enter the living HepG2 cells, and 1 mainly located in nucleus whereas 2 mainly distributed in cytoplasm. DNase and RNase digest tests indicated that both compounds could enter into the nucleus and interact with duplex DNA, especially, 2 could interact with RNA and/or G-quadruplex DNA. They also exhibited an obvious antiproliferative activity to HepG2 by using MTT assays, with IC50 values of 2.7 and 9.5 µM for 1 and 2, respectively.

Stimuli-responsive fluorescence switching of cyanostilbene derivatives: ultrasensitive water, acidochromism and mechanochromism.

A novel donor-π-acceptor structure stimuli-responsive fluorescent material of (Z)-2-(4'-(diphenylamino)-[1,1'-biphenyl]-4-yl)-3-(pyridin-2-yl)acrylonitrile (oN-TPA) was designed and synthesized, with the cyano-group and pyridine as the acceptors (A) and triphenylamine as the donor (D). oN-TPA exhibits an obvious solvatochromic effect and the excited state is confirmed to be a hybridized local and charge-transfer (HLCT) state that simultaneously possesses the locally-excited (LE) state and charge transfer (CT) state characters. The LE state ensures relatively high fluorescence efficiency while the CT state provides multi-stimuli responsive fluorescence behaviors because it is easily tuned by the surrounding environment. Firstly, oN-TPA exhibits "on-off-on" fluorescence properties in the mixture of water/tetrahydrofuran (THF) with the increasing water content. For the "on-off" part, a good linear relationship between fluorescence intensity and water fraction is achieved, which is ascribed to the synergistic effect of protons in water and intramolecular charge-transfer (ICT) effect depending on solvent polarity. The "off-on" part demonstrates the aggregation-induced enhanced emission (AIEE) character of oN-TPA. Secondly, oN-TPA can be used as a protonic acid sensor to detect trifluoroacetic acid (TFA) in solvent and HCl vapour in the solid state due to the binding of the proton to the pyridine group. Finally, oN-TPA presents remarkable and reversible mechanochromic fluorescence switching between 552 nm and 642 nm (90 nm red-shift) during the pressurizing-depressurizing process. This work not only comprehensively demonstrates the stimuli-responsive fluorescence behaviors of oN-TPA, but also provides a D-π-A structure fluorescent material possessing potential applications in detection and sensing with remarkable fluorescence changes.

Nucleic acid probe based on DNA-templated silver nanoclusters for turn-on fluorescence detection of tumor suppressor gene p53.

In this paper, we construct a fluorescence nucleic acid probe based on DNA-templated silver nanoclusters (DNA-Ag NCs) for the detection of the p53 gene. The fluorescence biosensing of the "turn-on" model is successfully implemented as a result of the target-triggered configurational change in the hairpin DNA probe and the synthesis of fluorescent Ag NCs. With this biosensor, the limit of detection (LOD) for the p53 gene is 3.57 nM and the linear range is 250-2500 nM in phosphate buffer solution, while a LOD of 6.06 nM in the linear range of 250-2500 nM is obtained in 1% diluted fetal calf serum. So this probe, with its advantages of specificity, practical application, easy operation and low cost, will have favourable development prospects in biological sensing and imaging.

Oral versus intravenous steroid therapy for relapses in patients with multiple sclerosis: an updated meta-analysis of six randomized controlled trials / Terapia oral versus intravenosa para recaídas de pacientes com esclerose múltipla: uma metanálise atualizada de seis ensaios clínicos randomizados

PURPOSE: To systematically evaluate whether oral steroids can be used with the same efficacy and safety in comparison with the intravenous regimen for treatment of multiple sclerosis relapses. METHOD: We searched Medline, Embase and Cochrane Library and systematically reviewed articles comparing outcomes of oral versus intravenous steroids for acute relapses in patients with a clinically definite diagnosis of multiple sclerosis. RESULTS: Six articles with 414 participants in total were analyzed. Five of the included trials reported the proportion of patients experiencing improvement in Expanded Disability Status Scale after receiving either oral or intravenous methylprednisolone treatment at four weeks; the pooled results showed that there was no statistically significant difference (OR 0.96; 95% CI 0.60, 1.54; p=0.86) between treatments. Three trials reported the detailed results of adverse events, indicating the two treatments appear to be equally safe. Two trials revealed that there was no significant difference in gadolinium enhancement activity on magnetic resonance imaging. One trial showed that the mean area under the concentration-time curve (AUC) at 24 and 48 hours did not differ between groups. CONCLUSION: No significant differences were found in terms of clinical (benefits and adverse events), radiological and pharmacological outcomes in multiple sclerosis relapses in patients after oral or intravenous steroids treatment. Our meta-analysis provides evidence that oral steroid therapy is not inferior to intravenous steroid therapy. Thus oral administration may be a favorable substitute for intravenous medication of multiple sclerosis relapses.

PROPÓSITO: Avaliar de forma sistemática se esteroides orais podem ser utilizados com a mesma eficácia e segurança em comparação com o regime intravenoso para o tratamento de recaídas da esclerose múltipla (MS). MÉTODO: Foram pesquisados Medline, Embase e Cochrane Library e sistematicamente revistos artigos comparando resultados de esteroides orais versus intravenosos para recaídas agudas em pacientes com diagnóstico de esclerose múltipla clinicamente definida. RESULTADOS: Seis artigos com 414 participantes no total foram analisados. Cinco dos estudos incluídos relataram a proporção de doentes com melhoria através de "Expanded Disability Status Scale" depois de receber um ou outro tratamento: metilprednisolona oral ou intravenosa por quatro semanas. Os resultados combinados mostraram que não houve diferença estatisticamente significativa (OR 0,96; 95% 101 0,60, 1,54 ; p = 0,86). Três estudos mostraram os resultados detalhados de eventos adversos, indicando que os dois tratamentos parecem ser igualmente seguros. Dois ensaios revelaram que não havia nenhuma diferença significativa no aumento de atividade de gadolínio via imagens por ressonância magnética. Um estudo mostrou que a área média sob as curvas de concentração-tempo (AUC) às 24 horas e 48 horas não diferiram entre os grupos. CONCLUSÃO: Não foram encontradas diferenças significativas em termos de clínicos (benefícios e eventos adversos) ou nos resultados radiológicos e farmacológicos em pacientes pós-esteroides por via oral ou intravenosa no tratamento de várias recaídas de esclerose. Nossa metanálise fornece evidências de que a terapia com esteroides por via oral não é inferior à terapia com esteroides por via intravenosa. Assim, a administração oral pode ser um substituto favorável para medicação intravenosa de recidivas da esclerose múltipla.