Dearomatization Silylation of Benzofurans and Furopyridines via Silyl Radical Addition and Endocyclic C-O Bond Scission.

Direct introduction of silyl radicals to forge C-Si bonds is of central importance in organic synthesis, owing to the formidable potential of silyl groups as coupling partners for further derivatization reactions to achieve more valuable compounds. Cleavage of heteroaromatic endocyclic carbon-heteroatom bonds to assemble C-Si bonds is scarce. Here, we demonstrate a dearomatization silylation of benzofurans and furopyridines via silyl radical addition and C(2)-O bond scission under metal-catalyst-free and mild conditions. Preliminary mechanistic experiments suggest that these transformations involve radical/single-electron transfer and [1,5]-Brook rearrangement processes. This protocol for the total synthesis of Doxepin and oxyresveratrol derivatives is carried out. The silylated products in several transformation reactions have proven to be useful as synthetic intermediates.

Nickel-Catalyzed Cross-Coupling Reaction of Aryl Methyl Sulfides with Aryl Bromides.

A nickel-catalyzed cross-coupling reaction of aryl methyl sulfides with aryl bromides has been developed to access biaryls in yields of up to 86%. The reactions proceeded well using Ni(COD)2 as catalyst with the ligand BINAP (2,2'-bis(diphenylphosphanyl)-1,1'-binaphthalene) in the presence of magnesium. The method has a broad scope of substrates and is scalable. The wide availability of commercially available aryl bromides and the absence of preparation and preparation of organometallic reagents make the reaction of high application value.

Posterior reversible encephalopathy syndrome secondary to acute post-streptococcal glomerulonephritis in a child: a case report from the Tibetan plateau.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a disorder of reversible vasogenic brain oedema with acute neurologic symptoms. It is a rare but serious disease that affects the central nervous system. PRES is a rare complication of acute post-streptococcal glomerulonephritis (APSGN). High altitude can accelerate vasogenic brain oedema by increasing cerebral blood flow (CBF), impairing cerebral autoregulation and promoting vascular inflammation. We report a case of PRES induced by acute post-streptococcal glomerulonephritis in a high-altitude environment. CASE PRESENTATION: A fourteen-year-old Tibetan girl presented with progressive headache with haematuria, facial swelling, dizziness and vomiting for 2 weeks as well as multiple episodes of tonic-clonic seizures for 14 h. She was diagnosed with APSGN based on laboratory tests and clinical symptoms. Brain magnetic resonance imaging (MRI) and computed tomography (CT) revealed bilateral frontal, parietal and occipital lesions that were compatible with the radiological diagnosis of PRES. The treatments included an antibiotic (penicillin), an antiepileptic drug, and hyperbaric oxygen (HBO) therapy. Follow-up MRI obtained 1 week after admission and CT obtained 4 weeks and 6 weeks after admission demonstrated complete resolution of the brain lesions. CONCLUSIONS: The case illustrates a rare occurrence of PRES following APSGN in a 14-year-old child in the Tibetan Plateau. The hypoxic conditions of a high-altitude setting might lower the cerebral autoregulation threshold and amplify the endothelial inflammatory reaction, thus inducing PRES in patients with APSGN. It is important to recognize the clinical and radiologic features of PRES, and adjuvant HBO therapy can promote rapid recovery from this condition in high-altitude areas.

Self-assembled ruthenium (II) metallacycles and metallacages with imidazole-based ligands and their in vitro anticancer activity.

Six tetranuclear rectangular metallacycles were synthesized via the [2+2] coordination-driven self-assembly of imidazole-based ditopic donor 1,4-bis(imidazole-1-yl)benzene and 1,3-bis(imidazol-1-yl)benzene, with dinuclear half-sandwich p-cymene ruthenium(II) acceptors [Ru2(µ-η4-oxalato)(η6-p-cymene)2](SO3CF3)2, [Ru2(µ-η4-2,5-dioxido-1,4-benzoquinonato)(η6-p-cymene)2](SO3CF3)2 and [Ru2(µ-η4-5,8-dioxido-1,4-naphtoquinonato)(η6-p-cymene)2](SO3CF3)2, respectively. Likewise, three hexanuclear trigonal prismatic metallacages were prepared via the [2+3] self-assembly of tritopic donor of 1,3,5-tri(1H-imidazol-1-yl)benzene with these ruthenium(II) acceptors respectively. Self-selection of the single symmetrical and stable metallacycle and cage was observed although there is the possibility of forming different conformational isomeric products due to different binding modes of these imidazole-based donors. The self-assembled macrocycles and cage containing the 5,8-dioxido-1,4-naphtoquinonato (donq) spacer exhibited good anticancer activity on all tested cancer cell lines (HCT-116, MDA-MB-231, MCF-7, HeLa, A549, and HepG-2), and showed decreased cytotoxicities in HBE and THLE-2 normal cells. The effect of Ru and imidazole moiety of these assemblies on the anticancer activity was discussed. The study of binding ability of these donq-based Ru assemblies with ctDNA indicated that the complex 9 with 180° linear 1 ligand has the highest bonding constant Kb to ctDNA.

Enhanced recovery after surgery promotes the postoperative recovery of lung and gastrointestinal function of pseudomyxoma peritonei. / åŠ é€Ÿåº·å¤å¤–ç§‘ä¿ƒè¿›è ¹è†œå‡é»æ¶²ç˜¤æœ¯åŽè‚ºä¸Žèƒƒè‚ é“åŠŸèƒ½çš„åº·å¤.

OBJECTIVES: Pseudomyxoma peritonei (PMP) is a rare low-grade malignant tumor, which is difficult to operate with many postoperative complications. In recent years, enhanced recovery after surgery (ERAS) has been greatly developed in the perioperative management of surgical diseases, and it plays an important role in improving the postoperative prognosis of surgical patients. This study was conducted to explore the application of ERAS in the perioperative management of PMP patients, and to study the effect of ERAS on postoperative respiratory and digestive tract complications. METHODS: We retrospectively analyzed clinical data of patients with PMP from January 2014 to December 2018. These patients were treated with surgery in our center and they were divided into an observation group and a control group. The patients in the control group didn't perform ERAS in perioperative period, and patients in the observation group was performed ERAS. Then, we analyzed and compared the postoperative pulmonary complications (PPC) and gastrointestinal function between the 2 groups. RESULTS: There was no significant difference in the incidence of atelectasis, pleural effusion, pulmonary infection and acute respiratory distress syndrome (ARDS) between the two groups, but the total incidence of PPC in the observation group was significantly lower than that in the control group (P=0.032). The incidence of postoperative gastrointestinal dysfunction (PGID) in the observation group was significantly lower than that in the control group (P=0.025), and the postoperative first exhaust time, first defecation time, oral feeding time, and albumin level in the observation group were all better than those in the control group (all P<0.05). CONCLUSIONS: ERAS can significantly reduce the incidence of postoperative PPC and PGID in the PMP patients and improve their postoperative recovery.

Cathepsin K Knockout Exacerbates Haemorrhagic Transformation Induced by Recombinant Tissue Plasminogen Activator After Focal Cerebral Ischaemia in Mice.

Severe haemorrhagic transformation (HT), a common complication of recombinant tissue plasminogen activator (rtPA) treatment, predicts poor clinical outcomes in acute ischaemic stroke. The search for agents to mitigate this effect includes investigating biomolecules involved in neovascularization. This study examines the role of Cathepsin K (Ctsk) in rtPA-induced HT after focal cerebral ischaemia in mice. After knockout of Ctsk, the gene encoding Ctsk, the outcomes of Ctsk+/+ and Ctsk-/- mice were compared 24 h after rtPA-treated cerebral ischaemia with respect to HT severity, neurological deficits, brain oedema, infarct volume, number of apoptotic neurons and activated microglia/macrophage, blood-brain barrier integrity, vascular endothelial growth factor (VEGF) expression and Akt-mTOR pathway activation. We observed that haemoglobin levels, brain oedema and infarct volume were significantly greater and resulted in more severe neurological deficits in Ctsk-/- than in Ctsk+/+ mice. Consistent with our hypothesis, the number of NeuN-positive neurons was lower and the number of TUNEL-positive apoptotic neurons and activated microglia/macrophage was higher in Ctsk-/- than in Ctsk+/+ mice. Ctsk knockout mice exhibited more severe blood-brain barrier (BBB) disruption, with microvascular endothelial cells exhibiting greater VEGF expression and lower ratios of phospo-Akt/Akt and phospo-mTOR/mTOR than in Ctsk+/+ mice. This study is the first to provide molecular insights into Ctsk-regulated HT after cerebral ischaemia, suggesting that Ctsk deficiency may disrupt the BBB via Akt/mTOR/VEGF signalling, resulting in neurological deficits and neuron apoptosis. Ctsk administration has the potential as a novel modality for improving the safety of rtPA treatment following stroke.

Cobalt(II)-Based Metal-Organic Framework as Bifunctional Materials for Ag(I) Detection and Proton Reduction Catalysis for Hydrogen Production.

A novel cobalt(II)-based metal-organic framework, Co-MB, was prepared by hydrothermal reaction of Co(NO3)2·6H2O, 3,3'-methylenediphthalic acid (H4mda), and 1,4-bis(imidazol-1-ylmethyl)-benzene in sodium hydroxide aqueous solution and structurally characterized. It shows a high stability in water within the pH range from 2.2 to 11.6, which could be used as a highly selective and sensitive luminescent sensor for Ag(I) detection in a luminescent enhancement manner, with LOD about 23 nM. Importantly, such stable Co-MB could also work as proton reduction catalyst for photodriven hydrogen production coupled with visible-light organic dyes as photosensitizer. The influence factors of hydrogen production including pH, TEA (triethylamine) contents, and kinds of organic dyes are studied in detail. Under optimal condition, the TON value was up to 5133 per cycle, and this Co-MB could also be reused at least 3 times.

Previous chronic symptomatic and asymptomatic cerebral hemorrhage in patients with acute ischemic stroke.

PURPOSE: Identifying previous chronic cerebral hemorrhage (PCH), especially asymptomatic cases in patients with ischemic stroke, is essential for proper antithrombotic management. The study aimed to further clarify the prevalence of PCH and the associated factors in patients with acute ischemic stroke using multi-modal neuroimaging including susceptibility-weighted MR imaging (SWI). METHODS: This was a retrospective cross-sectional study of 382 patients with acute ischemic stroke. All patients underwent 3.0-T MRI for cranial SWI, 1.5-T or 3.0-T conventional cranial MRI, and cranial CT. Patients found with PCH were matched 1:4 with patients without PCH. Clinical manifestation, computed tomography, conventional cranial MRI, and cranial SWI were used to determine PCH. Clinical and neuroimaging findings between the patients with symptomatic vs. asymptomatic PCH were compared. RESULTS: Thirty-six patients (36/382, 9.4%) were determined to have had a PCH. Of these 36 patients, 17 (17/36, 47.2%, or 17/382, 4.5%) had asymptomatic PCH. Multivariable analysis showed that serum total cholesterol (OR = 0.510, 95%CI 0.312-0.832, P = 0.007), cerebral microbleeds (OR = 6.251, 95%CI 2.220-17.601, P = 0.001), and antithrombotic drugs history (OR = 3.213, 95%CI 1.018-10.145, P = 0.047) were independently associated with PCH. Asymptomatic PCH had similar clinical and neuroimaging characteristics with symptomatic PCH. CONCLUSION: PCH is not uncommon in acute ischemic stroke patients. Total serum cholesterol, cerebral microbleeds on SWI, and history of antithrombotic drugs were independently associated with PCH in patients with acute ischemic stroke. Asymptomatic PCH, which is easier to be missed and has similar characteristics with symptomatic PCH, should draw much attention.

Plasma Levels of miR-125b-5p and miR-206 in Acute Ischemic Stroke Patients After Recanalization Treatment: A Prospective Observational Study.

INTRODUCTION: Multiple microRNAs (miRNAs) participate in the response to hypoxic/ischemic and ischemia-reperfusion events. However, the expression of these miRNAs in circulation from patients with acute ischemic stroke (AIS) receiving recanalization treatment has not been examined, and whether they are associated with the severity and outcome of stroke is still unknown. MATERIALS AND METHODS: In this prospective cohort study, plasma levels of miR-125b-5p, miR-15a-3p, miR-15a-5p, and miR-206 were measured at 24 hours after thrombolysis with or without endovascular treatment in 94 patients with AIS, as determined by qRT-PCR. Stroke severity was assessed based on National Institutes of Health Stroke Scale (NIHSS) score and infarct lesion. Intracranial haemorrhage (ICH) was recorded. An unfavorable outcome was defined as a modified Rankin Scale score greater than 2 at day 90 after stroke. RESULTS: miR-125b-5p and miR-206 levels were correlated with NIHSS scores (P = .014 and P = .002) and cerebral infarction volumes (P = .025 and P = .030). miR-125b-5p levels were significantly higher in patients with an unfavorable outcome than in patients with a favorable outcome (P = .002) and showed good diagnostic accuracy in discriminating the presence of an unfavorable outcome (area under the curve .735, 95% confidence interval .623-.829, P < .001). No association was found between different miRNAs and ICH. CONCLUSIONS: In AIS patients after thrombolysis with or without endovascular treatment, miR-125b-5p is a novel prognostic biomarker highly associated with an unfavorable outcome. miR-125b-5p and miR-206 levels are associated with stroke severity.

Structural changes of cerebellum and brainstem in migraine without aura.

BACKGROUND: Increasing evidence has suggested that the cerebellum is associated with pain and migraine. In addition, the descending pain system of the brainstem is the major site of trigeminal pain processing and modulation and has been discussed as a main player in the pathophysiology of migraine. Cerebellar and brainstem structural changes associated with migraineurs remain to be further investigated. METHODS: Voxel-based morphometry (VBM) (50 controls, 50 migraineurs without aura (MWoAs)) and diffusion tensor imaging (DTI) (46 controls, 46 MWoAs) were used to assess cerebellum and brainstem anatomical alterations associated with MWoAs. We utilized a spatially unbiased infratentorial template toolbox (SUIT) to perform cerebellum and brainstem optimized VBM and DTI analysis. We extracted the average diffusion values from a probabilistic cerebellar white matter atlas to investigate whether MWoAs exhibited microstructure alterations in the cerebellar peduncle tracts. RESULTS: MWoAs showed decreased fractional anisotropy (FA) in the vermis VI extending to the bilateral lobules V and VI of the cerebellum. We also found higher axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) in the right inferior cerebellum peduncle tract in MWoAs. MWoAs exhibited both reduced gray matter volume and increased AD, MD and RD in the spinal trigeminal nucleus (SpV). CONCLUSION: MWoAs exhibited microstructural changes in the cerebellum and the local brainstem. These structural differences might contribute to dysfunction of the transmission and modulation of noxious information, trigeminal nociception, and conduction and integration of multimodal information in MWoAs. These findings further suggest involvement of the cerebellum and the brainstem in the pathology of migraine without aura.

Electron-initiated low noise 1064 nm InGaAsP/InAlAs avalanche photodetectors.

We report an electron-initiated 1064 nm InGaAsP avalanche photodetectors (APDs) with an InAlAs multiplier. By utilizing a tailored digital alloy superlattice grading structure, a charge layer and a p type InAlAs multiplier, an unity gain quantum efficiency of 48%, a low room temperature dark current of 470 pA at 90% breakdown voltage, and a low multiplication noise with an effective k ratio of ∼0.2 are achieved. The measured maximum gain factor is 5 at room temperature, which is currently limited by the non-optimized electric field profiles, and can be readily enhanced by modifying the doping and thickness parameters for the multiplier and the charge layer.

Relationship between intracranial internal carotid artery calcification and enlarged cerebral perivascular space.

PURPOSE: The association between intracranial internal carotid artery (IICA) calcification and lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMBs) has been well researched. However, enlarged cerebral perivascular space (PVS) has not yet been reported to correlate with intracranial internal carotid artery calcification. Therefore, the primary aim of this study was to investigate the relationship between IICA calcification and enlarged PVS. METHODS: A total of 189 patients with ischemic stroke in the middle cerebral artery territory who presented within 7 days of ictus from 2012 to 2015 were enrolled respectively. All patients were required to have undergone head computed tomography, magnetic resonance imaging, susceptibility-weighted magnetic resonance imaging, magnetic resonance angiography, or computed tomography angiography. Clinical characteristics were recorded. IICA calcification and enlarged PVS were semi-quantitatively evaluated, and the presence of lacunes, WMH, and CMBs was recorded. RESULTS: Of the 189 patients, 63.5% were male. Mean age of the patients was 68.6 ± 12.2 years. There were 104 patients with IICA calcification. Age, diabetes mellitus, lacunes, and white matter hyperintensity were significantly associated with IICA calcification (P < 0.05). Multivariate logistic regression analysis showed that age, diabetes mellitus, and lacunes were independent predictors of IICA calcification (P < 0.05). A lower risk of IICA calcification was found in patients with a higher enlarged PVS score (P = 0.004). CONCLUSION: Higher enlarged PVS scores were associated with a lesser degree of IICA calcification. There appears to be a relationship between reduced risk of IICA calcification and enlarged PVS.

Synthesis and photophysical studies of self-assembled multicomponent supramolecular coordination prisms bearing porphyrin faces.

Multicomponent self-assembly, wherein two unique donor precursors are combined with a single metal acceptor instead of the more common two-component assembly, can be achieved by selecting Lewis-basic sites and metal nodes that select for heteroligated coordination spheres. Platinum(II) ions show a thermodynamic preference for mixed pyridyl/carboxylate coordination environments and are thus suitable for such designs. The use of three or more unique building blocks increases the structural complexity of supramolecules. Herein, we describe the synthesis and characterization of rectangular prismatic supramolecular coordination complexes (SCCs) with two faces occupied by porphyrin molecules, motivated by the search for new multichromophore complexes with promising light-harvesting properties. These prisms are obtained from the self-assembly of a 90° Pt(II) acceptor with a meso-substituted tetrapyridylporphyrin (TPyP) and dicarboxylate ligands. The generality of this self-assembly reaction is demonstrated using five dicarboxylate ligands, two based on a rigid central phenyl ring and three alkyl-spaced variants, to form a total of five free-base and five Zn-metallated porphyrin prisms. All 10 SCCs are characterized by (31)P and (1)H multinuclear NMR spectroscopy and electrospray ionization mass spectrometry, confirming the structure of each self-assembly and the stoichiometry of formation. The photophysical properties of the resulting SCCs were investigated revealing that the absorption and emission properties of the free-base and metallated porphyrin prisms preserve the spectral features associated with free TPyP.

Assessment of gray and white matter structural alterations in migraineurs without aura.

BACKGROUND: Migraine constitute a disorder characterized by recurrent headaches, and have a high prevalence, a high socio-economic burden and severe effects on quality of life. Our previous fMRI study demonstrated that some brain regions are functional alterations in migraineurs. As the function of the human brain is related to its structure, we further investigated white and gray matter structural alterations in migraineurs. METHODS: In current study, we used surface-based morphometry, voxel-based morphometry and diffusion tensor imaging analyses to detect structural alterations of the white matter and gray matter in 32 migraineurs without aura compared with 32 age- and gender-matched healthy controls. RESULTS: We found that migraineurs without aura exhibited significantly increased gray matter volume in the bilateral cerebellar culmen, increased cortical thickness in the lateral occipital-temporal cortex, decreased cortical thickness in the right insula, increased gyrification index in left postcentral gyrus, superior parietal lobule and right lateral occipital cortex, and decreased gyrification index in the left rostral middle frontal gyrus compared with controls. No significant change in white matter microstructure was found in DTI analyses. CONCLUSION: The significantly altered gray matter brain regions were known to be associated with sensory discrimination of pain, multi-sensory integration and nociceptive information processing and were consistent with our previous fMRI study, and may be involved in the pathological mechanism of migraine without aura.

The association of six non-synonymous variants in three DNA repair genes with hepatocellular carcinoma risk: a meta-analysis.

Hepatocellular carcinoma is a complex polygenic disease. Despite the huge advances in genetic epidemiology, it still remains a challenge to unveil the genetic architecture of hepatocellular carcinoma. We, therefore, decided to meta-analytically assess the association of six non-synonymous coding variants from XRCC1, XRCC3 and XPD genes with hepatocellular carcinoma risk by pooling the results of 20 English articles. This meta-analysis was conducted according to the PRISMA statement, and data collection was independently completed in duplicate. In overall analyses, the minor alleles of four variants, Arg280His (odds ratio, 95% confidence interval, P: 1.37, 1.13-1.66, 0.001), Thr241Met (1.93, 1.17-3.20, 0.011), Asp312Asn (1.22, 1.08-1.38, 0.001) and Lys751Gln (1.42, 1.02-1.97, 0.038), were associated with the significant risk for hepatocellular carcinoma. There were low probabilities of publication bias for all variants. Subgroup analyses revealed significant association of XRCC1 gene Arg399Gln with hepatocellular carcinoma in Chinese especially from south China (odds ratio, 95% confidence interval, P: 1.57, 1.16-2.14, 0.004), in larger studies (1.48, 1.11-1.98, 0.007) and in studies with population-based controls (1.33, 1.06-1.68, 0.016). Taken together, our findings demonstrated that XPD gene Asp312Asn and XRCC1 gene Arg399Gln might be candidate susceptibility loci for hepatocellular carcinoma. Considering the ubiquity of genetic heterogeneity, further validation in a broad range of ethnic populations is warranted.

Impact of etching on the surface leakage generation in mesa-type InGaAs/InAlAs avalanche photodetectors.

Effects of mesa etching and geometry on InGaAs/InAlAs avalanche photodiodes (APDs) were investigated by using both wet and inductively coupled plasma (ICP) etching with different mesa shapes as well as etchants. It was found that the mesa geometry had no evident impact on APDs' characteristics regardless of the etching techniques applied. Besides, ICP-etched APDs showed faster punch-through, suppressed premature surface breakdown and lower dark current behaviors compared to the wet-etched devices. Substantially suppressed surface leakage was also observed for ICP-etched devices, showing 1 and 3 orders of magnitude better at room temperature and 77 K respectively, and over 1 order of magnitude higher surface resistivity up to 4×107 Ω cm, in comparison to the wet-etched APDs. Introduction of extra hydrogen and Ar plasma in ICP etching led to detrimental effects to APDs' performance by enhancing the tunneling or recombination at surfaces. Those experimental results were clearly interpreted based on the surface state theories.

Synthesis of fluorinated carbazoles via C-H arylation catalyzed by Pd/Cu bimetal system and their antibacterial activities.

An effective intramolecular C-H arylation reaction catalyzed by a bimetallic catalytic system Pd(OAc)2/CuI for the synthesis of fluorine-substituted carbazoles from corresponding N-phenyl-2-haloaniline derivatives under ligand free conditions is demonstrated. The established method is effective for both N-phenyl-2-bromoaniline and N-phenyl-2-chloroaniline, and requires the low loading of Pd(OAc)2 (0.5 mol%). A series of new fluorinated carbazoles were synthesized in excellent yields using the protocol (>83%, 19 examples) and were fully characterized by (1)H, (13)C and (19)F NMR spectral data, HRMS and elemental analysis. All compounds were evaluated for their antibacterial activities against four bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and methicillin-resistant S. aureus with resistance to gentamicin) by serial dilution technique. All tested compounds showed antibacterial activity against three test strains (S. aureus, B. subtilis and MRSA), and most of these compounds displayed pronounced antimicrobial activities against these three strains with low MIC values ranging from 0.39 to 6.25 µg/mL. Among them, compounds 7 and 14 exhibited potent inhibitory activity better than reference drugs meropenem and streptomycin. Three compounds (2, 4 and 5) showed antibacterial activity against E. coli. with MIC values from 12.5 to 25 µg/mL.

Stereoselective Blockage of Quinidine and Quinine in the hERG Channel and the Effect of Their Rescue Potency on Drug-Induced hERG Trafficking Defect.

Diastereoisomers of quinidine and quinine are used to treat arrhythmia and malaria, respectively. It has been reported that both drugs block the hERG (human ether-a-go-go-related gene) potassium channel which is essential for myocardium repolarization. Abnormality of repolarization increases risk of arrhythmia. The aim of our research is to study and compare the impacts of quinidine and quinine on hERG. Results show that both drugs block the hERG channel, with quinine 14-fold less potent than quinidine. In addition, they presented distinct impacts on channel dynamics. The results imply their stereospecific block effect on the hERG channel. However, F656C-hERG reversed this stereoselectivity. The mutation decreases affinity of the two drugs with hERG, and quinine was more potent than quinidine in F656C-hERG blockage. These data suggest that F656 residue contributes to the stereoselective pocket for quinidine and quinine. Further study demonstrates that both drugs do not change hERG protein levels. In rescue experiments, we found that they exert no reverse effect on pentamidine- or desipramine-induced hERG trafficking defect, although quinidine has been reported to rescue trafficking-deficient pore mutation hERG G601S based on the interaction with F656. Our research demonstrated stereoselective effects of quinidine and quinine on the hERG channel, and this is the first study to explore their reversal potency on drug-induced hERG deficiency.

Increased default mode network connectivity and increased regional homogeneity in migraineurs without aura.

BACKGROUND: The precuneus/posterior cingulate cortex, which has been associated with pain sensitivity, plays a pivotal role in the default mode network. However, information regarding migraine-related alterations in resting-state brain functional connectivity in the default mode network and in local regional spontaneous neuronal activity is not adequate. METHODS: This study used functional magnetic resonance imaging to acquire resting-state scans in 22 migraineurs without aura and in 22 healthy matched controls. Independent component analysis, a data-driven method, was used to calculate the resting-state functional connectivity of the default mode network in the patient and healthy control groups. Regional homogeneity (ReHo) was used to analyse the local features of spontaneous resting-state brain activity in the migraineurs without aura. RESULTS: Compared with the healthy controls, migraineurs without aura showed increased functional connectivity in the left precuneus/posterior cingulate cortex within the default mode network and significant increase in ReHo values in the bilateral precuneus/posterior cingulate cortex, left pons and trigeminal nerve entry zone. In addition, functional connectivity was decreased between the areas with abnormal ReHo (using the peaks in the precuneus/posterior cingulate cortex) and other brain areas. CONCLUSIONS: The abnormalities in the precuneus/posterior cingulate cortex suggest that migraineurs without aura may exhibit information transfer and multimodal integration dysfunction and that pain sensitivity and pian processing may also be affected.

Construction of luminescent dye@MOF platforms for sensing antibiotics with enhanced selectivity and sensitivity.

The fabrication of luminescent dye@MOF composites has received extensive attentions in the development of realistic sensing applications. Herein, based on two anionic In-MOFs with different pore structure (1 and 2), the charge and size dependent ion-exchange of cationic dyes was investigated, and consequently four luminescent dye@MOF composites (DMASM@1/2 and RhB@1/2) were successfully fabricated and importantly can be regarded as ideal platforms for better understanding of the factors affecting the construction of dye@MOF composites, which may closely related to a well match between the intrinsic properties and size/charge of the fluorescent molecules and the porosity, structure character of the MOF hosts. Furthermore, these four dye@MOF composites were utilized for sensing of different kinds of antibiotics, demonstrating enhanced selectivity and sensitivity. DMASM@1/2 demonstrated excellent selectivity and sensitivity for NFT and NFZ antibiotics, while RhB@1/2 exhibited excellent selectivity and sensitivity for MDZ and DTZ antibiotics. Systematic analysis of the detection mechanism revealed that different energy transfer efficiency and interaction between MOF frameworks and different types of guest dyes led to different selectivity and detection mechanisms for antibiotics. Moreover, high selectivity and sensitivity, low LOD and extraordinary recycling capacity of four dye@MOF composites in the detection of antibiotics promote their excellent prospect in the further practical application.