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Background: The causes of migraine remain unclear. Evidence suggests that the MAPK and PI3K/Akt signaling pathways play a role in migraine pathogenesis. However, studies on genetic polymorphisms in the two pathways associated with migraine are still limited. Methods: This study included 226 migraineurs and 452 age‐ and sex‐matched nonmigraine control individuals. Genotyping of 31 Single Nucleotide Polymorphisms (SNPs) in 21 genes was performed. The relationship between migraine and gene polymorphisms was analyzed by using logistic regression. SNP–SNP interactions were examined by a generalized multifactor dimension reduction (GMDR) approach. The possible role of SNPs was evaluated with gene expression data from the GTEx database. Results: The RASGRP2‐rs2230414 GT genotype was associated with decreased migraine risk compared with the wild‐type GG genotype [ORadj (95% CI): 0.674(0.458–0.989)]. PIK3R1‐rs3730089 was associated with migraine in the recessive model [ORadj (95% CI): 1.446(1.004–2.083)]. The CACNA1H‐rs61734410 CT genotype was associated with migraine risk [ORadj (95% CI): 1.561(1.068–2.281)]. One significant two‐way SNP–SNP interaction was found (PRKCA rs2228945‐BDNF rs6265) (p = 0.0107). Significant eQTL and sQTL signals were observed for the SNP rs2230414. Conclusions: This is the first study to systematically reveal significant associations between MAPK and PI3K/Akt signaling pathway‐related gene polymorphisms and migraine risk. [ABSTRACT FROM AUTHOR]

Aim: Systemic amyloidosis is a condition in which misfolded amyloid fibrils are deposited within tissues. Amyloid myopathy is a rare manifestation of systemic amyloidosis. However, whether skeletal muscle involvement is underestimated and whether such deposition guarantees clinical and pathological myopathic features remain to be investigated. Methods: We retrospectively reviewed patients with systemic amyloidosis, in whom skeletal muscle biopsies were performed at our centre between January 2018 and June 2023. In total, 28 patients with suspected systemic amyloidosis were included. Among these, 21 presented with cardiomyopathy but lacked myopathic symptoms. The clinical and pathological data of these patients were further analysed. The amyloid type was confirmed by immunohistochemistry. Results: Twenty‐eight patients with suspected systemic amyloidosis underwent muscle biopsy. Amyloid deposition in the skeletal muscle was confirmed in 24 patients, including 22 with light‐chain amyloidosis (AL) and two with transthyretin amyloidosis (ATTR). Among the 24 patients, seven presented with muscle weakness and decreased muscle strength (Group 1, symptomatic myopathy), whereas the remaining 17 exhibited normal muscle strength (Group 2, asymptomatic myopathy). Group 1 included four patients with AL‐λ, one with AL‐κ and two with ATTR. Group 2 included 15 patients with AL‐λ and two patients with AL‐κ. In Group 1, six patients exhibited neuropathy, whereas only one patient in Group 2 presented with subclinical neuropathy on nerve conduction studies. Amyloid deposition in the interstitium was the most obvious change, observed in all 24 patients. Neuropathic changes, including denervation atrophy and muscle fibre grouping, were also common. Except for type 2 fibre atrophy, the other myopathic changes were mild and nonspecific. No sarcolemmal disruption was observed. Immunohistochemical analysis revealed marked positivity for MAC and MHC1 expression in the regions with amyloid deposits. Clinicopathological analysis revealed no significant differences in the extent of muscular amyloid deposition between the two groups. Nevertheless, patients in Group 1 displayed more pronounced neurogenic atrophy on skeletal muscle biopsies. Conclusions: Our study indicates that amyloid deposition in skeletal muscle is commonly observed but rarely causes symptomatic myopathy in systemic amyloidosis. [ABSTRACT FROM AUTHOR]

Colorful afterglow materials have promising applications in optoelectronic displays. To effectively fine‐tune the afterglow color, an assembly structure that includes UV lamp, persistent room temperature phosphorescence (pRTP) layer, and fluorescent layer (from the bottom to the top) with superimposition of pRTP and fluorescence, is designed. The fluorescence component is emitted from a PMMA film doped with asymmetric 4‐(7‐methoxy‐5,6‐dinitrobenzo[c][1,2,5,]thiadiazol‐4‐yl)‐N,N‐diphenylaniline (TPA‐TD), which has a broad absorption that covers the entire visible region, facilitating effective radiative energy transfer between various pRTP materials and TPA‐TD. Due to its aggregation‐induced‐emission nature, the fluorescence intensity of TPA‐TD enhances with increased doping concentration in PMMA films. Meanwhile, the transmission of TPA‐TD film reduces as the doping concentration increases, which results in a reduction of pRTP intensity through the TPA‐TD film. Therefore, the afterglow color can be fine‐tuned in situ by regulating the ratio of pRTP and fluorescence. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the utility of hippocampal radiomics using multiparametric simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) for early diagnosis of Alzheimer's disease (AD). Methods: A total of 53 healthy control (HC) participants, 55 patients with amnestic mild cognitive impairment (aMCI), and 51 patients with AD were included in this study. All participants accepted simultaneous PET/MRI scans, including 18F‐fluorodeoxyglucose (18F‐FDG) PET, 3D arterial spin labeling (ASL), and high‐resolution T1‐weighted imaging (3D T1WI). Radiomics features were extracted from the hippocampus region on those three modal images. Logistic regression models were trained to classify AD and HC, AD and aMCI, aMCI and HC respectively. The diagnostic performance and radiomics score (Rad‐Score) of logistic regression models were evaluated from 5‐fold cross‐validation. Results: The hippocampal radiomics features demonstrated favorable diagnostic performance, with the multimodal classifier outperforming the single‐modal classifier in the binary classification of HC, aMCI, and AD. Using the multimodal classifier, we achieved an area under the receiver operating characteristic curve (AUC) of 0.98 and accuracy of 96.7% for classifying AD from HC, and an AUC of 0.86 and accuracy of 80.6% for classifying aMCI from HC. The value of Rad‐Score differed significantly between the AD and HC (p < 0.001), aMCI and HC (p < 0.001) groups. Decision curve analysis showed superior clinical benefits of multimodal classifiers compared to neuropsychological tests. Conclusion: Multiparametric hippocampal radiomics using PET/MRI aids in the identification of early AD, and may provide a potential biomarker for clinical applications. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is endowed with a highly aggressive nature that results in distant metastases and high recurrence rates, yet limited success is realized in traditional chemotherapy. Activatable photosensitizers (PSs) may provide an effective and non‐invasive strategy to induce TNBC cell death in a precise way by offering stimuli‐responsive reactive oxygen species (ROS). However, the toxicity of ROS is often mitigated and even devitalized by the instinctive behavior of ROS resistance in TNBC cells. To address this issue, herein a small molecular self‐assembly nano‐prodrug is presented to co‐deliver an activatable PS and ROS resistance inhibitor. In TNBC cells, the overexpressed glutathione can disassemble the nano‐prodrug, thereby releasing ROS resistance inhibitor and activating the PS for photodynamic therapy and fluorescence imaging. A hybrid membrane coating‐assisted nanoparticle formation strategy is further demonstrated for efficient inhibition of tumor growth and distant metastases on both subcutaneous and orthotopic TNBC mice models. [ABSTRACT FROM AUTHOR]

Understanding the diffusion law of cement slurry is the key to analyzing and evaluating the reinforcement effect of grouting. This study aimed to reveal the flow grouting mechanism of slurry in the reserved space between piles and soil and the penetration diffusion rule of slurry in the soil around the piles. For this purpose, the grouting slurry was regarded as a Newtonian fluid. The Navier–Stokes equations of fluid mechanics and renormalization group k–ε model were used to study the flow diffusion of slurry in the reserved space around a pile for grouting the drilling with prestressed concrete pipes. The permeability of soil slurry was determined using Darcy's law, and the flow field of slurry during grouting was numerically simulated. The results showed that the flow velocity of slurry and the reinforcement effect of grouting decrease gradually as the flow path extends. The radial flow of slurry in the grouting pipe shows a clear trend of circumferential diffusion. The slurry thickness in the reserved space for grouting decreases with an increase in the distance from the grouting outlet. Its attenuation trend becomes more obvious with increasing grouting height. The grouting thickness directly reflects the filling effect of slurry and is an important index to evaluate the grouting effect of drilling with prestressed concrete pipes. [ABSTRACT FROM AUTHOR]

Thermokarst terrain is developing at an accelerating pace in the ice‐rich permafrost on the Qinghai–Tibet Plateau (QTP), China, and the most dramatic of these terrain‐altering thermokarsts is retrogressive thaw slump (RTS). The freeze–thaw erosion (FTE) impacts are sharply increasing on the Plateau due to RTS, especially as a result of the migration of fine sediments in cold climates, these impacts are still not quantified due to the limitation of hydro‐thermal‐mass transport laws in RTS development. Moreover, it is difficult to assess the impact of RTS on the ecology and environment, especially on soil erosion. This study developed a heat–water‐mass transport coupled model of a RTS in the Beiluhe River Region on the QTP, considering the actual topography, water‐ice phase change, latent heat, and surface heat exchange layer. Based on the observed data of ground temperature, unfrozen water content, and heat flux, the coupled model herein is practicable for presenting the geotemperature regime and groundwater flow in the RTS area, thereby quantifying the ice‐rich permafrost thaw and mass wasting. The results presented indicate that: (1) the seepage velocity of the superficial zone (0–1.5 m depth) is two orders of magnitude higher than that of the permafrost table; (2) the mean ice‐rich permafrost thaw volume was 13.4 m2 from 2016 to 2021; and (3) the cumulative mass transport volume was 22 m2 from July 2020 to September 2021. In addition, the relation between the FTE (shown as the migration of sediments) and the amount of ground ice ablation can be fitted by an exponential equation. This work proposes a reliable method for quantifying the effect of FTE and is helpful to assess the eco‐environmental impacts of RTS. [ABSTRACT FROM AUTHOR]

The mechanisms underlying ischemic infarction in patients with vertebrobasilar dolichoectasia (VBD) remain unclear. In this study, we retrospectively analyzed the imaging characteristics of high‐resolution magnetic resonance imaging (HR‐MRI) in patients with VBD to explore the possible mechanisms of ischemic stroke (IS) in patients with VBD. Patients with VBD were recruited from the HR‐MRI database between July 2017 and June 2021. HR‐MRI was used to evaluate the diameter, bifurcation height, laterality, arterial dissection, and atherosclerotic plaques of the basilar artery (BA). Transcranial Doppler was used to measure the vertebrobasilar mean velocity (Vm), peak systolic velocity (Vs), end‐diastolic velocity (Vd), and pulsatile index. Twenty‐six patients with VBD were enrolled, of which 15 had IS and 11 did not. The incidence of classical vascular risk factors, including age, sex, hypertension, diabetes, and hypercholesterolemia, did not differ significantly between the two groups. The BA diameters of the stroke group were significantly higher than that of the nonstroke group (6.57 ± 1.00 mm vs. 5.06 ± 0.50 mm, p = 0.000). The height of the BA bifurcation in the stroke and nonstroke groups was statistically significant (p = 0.002). Compared with the nonstroke group, the Vm, Vs, and Vd of the BA in the stroke group were lower, but the difference was not significant. In the 16 patients with atherosclerotic stenosis, 30 atherosclerotic plaques were found in the BA, 18 (60%) in the greater curvature, and 12 (40%) in the lesser curvature. In addition, one artery dissection (on the lesser curvature) and two dissecting aneurysms (on the greater curvature) were found in the BA of three patients, respectively. The BA diameter and bifurcation height are factors related to IS in patients with VBD. The mechanism of stroke in patients with VBD may involve abnormal hemodynamics, artery dissection, and atherosclerosis. HR‐MRI is a useful method for evaluating the risk and underlying mechanism of stroke in patients with VBD. [ABSTRACT FROM AUTHOR]

Background and purpose: The presence of apolipoprotein E ε4 (APOE ε4) is associated with an increased risk of developing Alzheimer disease (AD). The aim of this study was to assess the effects of APOE ε4 on amyloid‐β (Aβ) pathology, glucose metabolism, and gray matter (GM) volume and their longitudinal changes in healthy control (HC) and amnestic mild cognitive impairment (aMCI). Methods: We included 50 HCs and 109 aMCI patients from the Alzheimer's Disease Neuroimaging Initiative phase 2/GO based on availability of baseline T1‐weighted magnetic resonance imaging, 18F‐florbetapir positron emission tomography (PET), and 18F‐fluorodeoxyglucose (FDG) PET. Of these, 35 HCs and 67 aMCI patients who underwent 24‐month scans were included for follow‐up study. Results: Voxelwise analysis revealed that APOE ε4 carriers exhibited greater baseline Aβ deposition than APOE ε4 noncarriers in both diagnostic groups. However, there was no significant difference between APOE ε4 noncarriers and APOE ε4 carriers in terms of 18F‐FDG PET standardized uptake value ratio and GM volume. Region of interest‐based analysis showed statistically significant greater Aβ deposition in APOE ε4 carriers than APOE ε4 noncarriers only in aMCI patients. Furthermore, APOE ε4 carriers generally exhibited a greater magnitude and spatial extent of longitudinal changes in Aβ deposition than APOE ε4 noncarriers in both diagnostic groups. Conclusions: Our findings suggest a differential effect of APOE ε4 on Aβ pathology, glucose metabolism, and GM volume. Studying APOE ε4‐related brain changes with neuroimaging biomarkers in preclinical AD offers an opportunity to further our understanding of the pathophysiology of AD at an early stage. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical features of Han Chinese patients with anti‐neurofascin‐155 (NF155) antibody‐positive neuropathy. Methods: We screened 194 patients with peripheral neuropathy for NF155 antibodies using a cell‐based assay (CBA) and teased‐fiber immunofluorescence assay. We summarized the clinical findings of seropositive patients. Results: The sera from 17 patients reacted to human embryonic kidney 293 cells transfected with NF155. Eleven of these patients had the immunoglobulin G (IgG) 4 isotype, a younger onset age, tremor, higher levels of cerebrospinal fluid protein, a larger diameter of the lumbosacral nerve root on magnetic resonance imaging, and the distal demyelinating symmetric phenotype. Most patients responded to steroids and rituximab. For the remaining six seropositive patients in CBA, the predominant antibody isotype was IgG3, IgG1, or undetectable, and only one patient with IgG3 showed a positive result in the teased‐fiber immunofluorescence assay. These patients did not share the typical features displayed by patients with the IgG4 isotype. Interpretation: In the Han Chinese population, a significant proportion of patients who fulfilled the criteria for chronic inflammatory demyelinating polyradiculoneuropathy diagnosis had anti‐NF155 IgG4 antibody‐positive neuropathy and displayed specific phenotypes. Ambiguous staining patterns may appear, and the potential for false positivity should be considered. For patients who presented with specific phenotypes, identifying antibodies and subtypes involved a significant laboratory workup. [ABSTRACT FROM AUTHOR]

Objectives: Epileptic patients suffer from seizure recurrence after surgery due to the challenging localization. Improvement of the noninvasive imaging‐based approach for a better definition of the abnormalities would be helpful for a better outcome. Methods: The quantitative anisotropy (QA) of diffusion spectrum imaging (DSI) is a quantitative scalar of evaluating the water diffusivity. Herein, we investigated the association between neuronal diameters or density acquired in literature and QA of DSI as well as the seizure localization in temporal lobe epilepsy. Thirty healthy controls (HCs) and 30 patients with hippocampal sclerosis (HS) were retrospectively analyzed. QA values were calculated and interactively compared between the areas with different neuronal diameter/density acquired from literature in the HCP‐1021 template. Diagnostic tests were performed on Z‐transformed asymmetry indices (AIs) of QA (which exclude physical asymmetry) among HS patients to evaluate its clinical value. Results: The QA values in HCs conformed with different pyramidal cell distributions ranged from giant to small; corresponding groups were the motor‐sensory, associative, and limbic groups, respectively. Additionally, the QA value was correlated with the neuronal diameter/density in cortical layer IIIc (correlation coefficient with diameter: 0.529, p = 0.035; density: −0.678, p = 0.011). Decreases in cingulum hippocampal segments (Chs) were consistently observed on the sclerosed side in patients. The area under the curve of the Z‐transformed AI in Chs to the lateralization of HS was 0.957 (sensitivity: 0.909, specificity: 0.895). Interpretation: QA based on DSI is likely to be useful to provide information to reflect the neuronal diameter/density and further facilitate localization of epileptic tissues. [ABSTRACT FROM AUTHOR]

Purpose: To assess the trend patterns and gender disparity in global burden of vision loss due to diabetic retinopathy (DR) by year, age, region and socioeconomic status using prevalence and years lived with disability (YLDs) from Global Burden of Disease (GBD) study 2017. Methods: Prevalence and YLDs data of vision loss attributable to DR were extracted from GBD Study 2017 in 195 countries and territories. Socio‐demographic Index (SDI) in 2017 was cited as indicators of socioeconomic status. Kruskal–Wallis test, Dunn's multiple comparisons and Pearson linear correlation were adopted to evaluate the gender disparity and association with socioeconomic levels. Results: Globally, total age‐standardized prevalence and YLDs rates of vision loss due to DR peaked around 2005, with prevalence rate of 58.98 [95% uncertainty interval (UI) 50.95–68.56] and YLDs rate of 5.00 (95% UI 3.51–6.84) per 100 000 population, respectively. The burden were expected to increase to 65.74 (95% UI 60.14–70.86) and 5.68 (95% UI 4.07–7.22) by 2050. The burden would increase according to our projection based on current epidemiological situation. However, gender disparity has existed since 1990 and been enlarging in recent years, with female being more heavily impacted. This pattern remained with ageing among different stages of vision impairments and varied through GBD super regions. Gender difference (females minus males) of age‐standardized prevalence rates was positively related to SDI (r = 0.1661, p = 0.0203). Diabetes has become a more important risk over the past 3 decades among the leading causes of vision loss. Conclusions: The DR‐related vision loss burden tended to increase under ageing population according to our projection with significant gender disparity. Public awareness of DR and gender sensitive health policy should be emphasized. [ABSTRACT FROM AUTHOR]

Purpose: To conduct a detailed analysis on the burden of vision loss due to diabetic retinopathy (DR) by year, age and gender in China from 1990 to 2017. Methods: This is a between‐country, retrospective, comparative burden‐of‐disease study. Prevalence and Years Lived with Disability (YLDs) data caused by DR in China and relative territories were extracted from the Global Burden of Disease (GBD) study 2017 to observe the changing trends of vision loss. Results: Prevalence and YLDs of DR in China increased significantly from 1990 to 2017. The age‐standardized prevalence and YLDs rate witnessed a slowly declining trend recently. Higher prevalence and YLDs were observed in female subjects in the past three decades. Middle‐aged and elderly people suffered from a higher burden of DR‐induced vision loss. The total age‐standardized prevalence rate of China in 1990 (17.68) and 2017 (21.88) was lower than that of other seven neighbouring countries. In 2017, moderate vision loss (MVL) (17.19) accounted for the largest proportion in China. The all‐age YLDs of DR showed the second‐highest increase (150.26%) while the age‐standardized YLDs rate showed the third‐highest increase (14.91%) among fifteen common causes of vision impairment (VI) from 1990 to 2017. China ranked 3rd among G20 countries in terms of all‐age YLDs while ranked 18th in age‐standardized YLDs rate in 2017. Conclusions: In the past three decades, the prevalence and YLDs due to DR in China have improved in both genders. This study highlights the importance of prevention for DR, especially for women and the elderly. [ABSTRACT FROM AUTHOR]

Objective: Altered functional activities and hypometabolism have been found in medial temporal lobe epilepsy patients with hippocampal sclerosis (mTLE‐HS). Hybrid PET/MR scanners provide opportunities to explore the relationship between resting‐state energy consumption and functional activities, but whether repeated seizures disturb the bioenergetic coupling and its relationship with seizure outcomes remain unknown. Methods: 18F‐FDG PET and resting‐state functional MRI (rs‐fMRI) scans were performed with hybrid PET/MR in 26 patients with mTLE‐HS and in healthy controls. Energy consumption was quantified by 18F‐FDG standardized uptake value ratio(SUVR) relative to cerebellum. Spontaneous neural activities were estimated using regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF) from rs‐fMRI. Between‐group differences in SUVR and rs‐fMRI derived metrics were evaluated by two‐sample t test. Voxel‐wise spatial correlations were explored between SUVR and ReHo, fALFF across gray matter and compared between groups. Furthermore, the relationships between altered fALFF/SUVR and ReHo/SUVR coupling and surgical outcomes were evaluated. Results: Both the patients and healthy controls showed significant positive correlations between SUVR and rs‐fMRI metrics. Spatial correlations between SUVR and fMRI‐derived metrics across gray matter were significantly higher in patients with mTLE‐HS compared with healthy controls (fALFF/SUVR, P < 0.001; ReHo/SUVR, P = 0.022). Higher fALFF/SUVR couplings were found in patients who had Engel class IA after surgery than all other (P = 0.025), while altered ReHo/SUVR couplings (P = 0.097) were not. Conclusion: These findings demonstrated altered bioenergetic coupling across gray matter and its relationship with seizure outcomes, which may provide novel insights into pathogenesis of mTLE‐HS and potential biomarkers for epilepsy surgery planning. [ABSTRACT FROM AUTHOR]

Background: White matter (WM) blood oxygenation level-dependent (BOLD) signals are reported to be related to neural activity. However, sensitivity of WM BOLD signals to disease remains unclear.Purpose: To investigate WM BOLD signal changes, directional variations of resting-state correlations in sensorimotor system in patients with pontine strokes, and to determine the relationship between WM BOLD signals and motor deficits.Study Type: Prospective.Subjects: Ethical approval was obtained from the local Ethics Committee and each participant gave written informed consent. Sixteen patients with focal pontine lesions and 16 age-matched control subjects were included.Field Strength/sequence: 3.0T T1 -weighted anatomic images using a 3D magnetization-prepared rapid gradient-echo sequence. Resting-state fMRI images using gradient-echo echo-planar imaging sequence. Diffusion-weighted images using single-shot spin-echo diffusion echo-planar imaging.Assessment: Relevant WM tracts in the sensorimotor system by region of interest-wise analysis were identified. Power spectra of BOLD signals and anisotropy of resting-state correlations were measured in sensorimotor system and compared between two groups. Their relationships with clinical scores were analyzed.Statistical Tests: Two-sample t-test; partial correlation analysis.Results: Power spectra of BOLD signals in nerve tracts on the ipsilesional side were significantly decreased (P < 0.05). Compared with that in healthy subjects, the anisotropy of resting-state correlations along identified WM tracts was decreased in the thalamus-dorsolateral prefrontal cortex bundle on the contralesional side, and all nerve tracts on the ipsilesional side. Partial least squares regression analysis showed the predicted outcome scores correlated significantly with actual Fugl-Meyer scores (R2  = 0.944, P = 0.013).Data Conclusion: Our findings suggest that disrupted activity and functional connectivity in WM areas of the sensorimotor system can be detected in pontine strokes, and may serve as a biomarker for motor function prediction.Level Of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:478-486. [ABSTRACT FROM AUTHOR]

Abstract: Aggregation‐induced emission/aggregation‐induced emission enhancement (AIE/AIEE) has recently attracted intense research, and a large number of AIE/AIEE luminogens (AIE/AIEEgens) have been constructed for application in diverse scientific fields. The AIE and AIEE effects have similar, but not identical, photophysical behaviors, which are closely related to molecular architectures. However, the current understanding of the inherent differences between AIE and AIEE is still obscure. Herein, a rational design strategy is reported for achieving AIE and AIEE effects by simply incorporating different substituents at the periphery of the same core skeleton. Experimental and theoretical studies on the series of compounds indicated that the restriction of intramolecular twisting motions or/and rotations plays an important role in regard to the corresponding AIE or AIEE behaviors. Moreover, compound 1 a (FW=203, ΦF=80.9 %) was discovered as the lowest molecular weight AIEEgen with a high quantum yield in the solid state despite having no rotatable units. Compound 2 a also exhibited an AIEE effect with the minimum necessary structure (a single ring). [ABSTRACT FROM AUTHOR]

Antibiotic-producing microorganisms have evolved several self-resistance mechanisms to prevent auto-toxicity. Overexpression of specific transporters to improve the efflux of toxic antibiotics has been found one of the most important and intrinsic resistance strategies used by many Streptomyces strains. In this work, two ATP-binding cassette (ABC) transporter-encoding genes located in the natamycin biosynthetic gene cluster, scnA and scnB, were identified as the primary exporter genes for natamycin efflux in Streptomyces chattanoogensis L10. Two other transporters located outside the cluster, a major facilitator superfamily transporter Mfs1 and an ABC transporter NepI/II were found to play a complementary role in natamycin efflux. ScnA/ScnB and Mfs1 also participate in exporting the immediate precursor of natamycin, 4,5-de-epoxynatamycin, which is more toxic to S. chattanoogensis L10 than natamycin. As the major complementary exporter for natamycin efflux, Mfs1 is up-regulated in response to intracellular accumulation of natamycin and 4,5-de-epoxynatamycin, suggesting a key role in the stress response for self-resistance. This article discusses a novel antibiotic-related efflux and response system in Streptomyces, as well as a self-resistance mechanism in antibiotic-producing strains. [ABSTRACT FROM AUTHOR]

Vitiligo is an acquired depigmenting disorder affecting 0.5-2% of the population worldwide, and as many as half of these cases develop before the age of 20 years.1 There are few Asian studies characterising the epidemiology of paediatric patients with vitiligo. Topical therapies included topical corticosteroids (mometasone 0.1% furoate cream, betamethasone 0.025% valerate cream, desonide 0.05% cream) and topical calcineurin inhibitors (tacrolimus 0.1% ointment, tacrolimus 0.03% ointment, pimecrolimus 1% cream). Of the 72 patients with documented outcomes, there was good response in 9 patients (12.5%), partial response in 50 (69.4%) patients and poor response in 13 (18.1%) patients. [Extracted from the article]

Background Nontuberculous mycobacterium ( NTM) infections are rare in children, with limited published studies. The course of the disease can be variable and there are no accepted treatment guidelines for the management of NTM infections in children. Objective To review a cohort of pediatric patients admitted to a tertiary pediatric hospital in Singapore for cutaneous NTM infections. Methods A retrospective review was performed of all children admitted to KK Women's and Children's Hospital with cutaneous NTM infections from 2002 to 2012. Results Sixty-seven patients with positive NTM cultures from various body sites were identified. Eight of the 67 patients (11.9%) presented with cutaneous NTM without evidence of systemic involvement. The mean age at diagnosis for these eight patients was 10 years (range 5-21 yrs). Mycobacterium abscessus was the most common NTM isolated (five patients), followed by Mycobacterium hemophilium (two patients) and Mycobacterium kansasii (one patient). Most patients presented with isolated skin abscesses. Two patients were immunocompromised. Six patients required multidrug antibiotic treatment for a median duration of 5.5 months (range 3-17 mos). The median follow-up duration was 8.5 months (range 2 wks-29 mos). Conclusion Although the incidence of cutaneous NTM is rare, the diagnosis should be considered in patients presenting with chronic wounds. Most patients require treatment with multidrug antibiotic therapy, although uncomplicated abscesses can be treated with surgical incision and drainage alone. [ABSTRACT FROM AUTHOR]

Aim To describe an Asian population with isolated cutaneous Langerhans cell histiocytosis ( LCH), presenting a review on previous studies on this subgroup of patients and comparing our cohort with other studies of cutaneous LCH with systemic involvement. Methods All patients diagnosed as LCH with cutaneous involvement presenting to a tertiary paediatric hospital ( KK Women's & Children's Hospital) between January 2001 and December 2011 were reviewed. Information recorded included clinical presentation, investigation results, treatment and outcome. Results We identified 10 patients with cutaneous manifestations of LCH. Six had isolated cutaneous LCH with no visceral or bony involvement, while four had cutaneous lesions with involvement of other organ systems. Of the patients with isolated skin involvement, three were treated with surgical excision, one with topical corticosteroids and two with multi-agent chemotherapy. The four patients with concomitant systemic involvement were treated with multi-agent chemotherapy. None of our patients with isolated cutaneous LCH progressed to multisystem disease during the follow-up period. Conclusion Cutaneous LCH, with or without other organ involvement at diagnosis has a good overall prognosis. However, long-term follow-up is recommended in view of possible recurrence. [ABSTRACT FROM AUTHOR]

In many types of tumours, especially pancreatic adenocarcinoma, miR-301a is over-expressed. This over-expression results in negative regulation of the target gene of miR-301a, the nuclear factor-κB ( NF-κB) repressing factor ( NKRF), increasing the activation of NF-κB and production of NF-κB-responsive pro-inflammatory cytokines such as interleukin-8, interferon-β, nitric oxide synthase 2A and cytochrome oxidase subunit 2 ( COX-2). However, in immune cells, mechanisms that regulate miR-301a have not been reported. Similar to tumour cells, Toll-like receptor ( TLR) -activated macrophages produce NF-κB-responsive pro-inflammatory cytokines. Therefore, it is of considerable interest to determine whether miR-301a regulates the secretion of cytokines by immune cells. In the present study, we demonstrate that the expression of miR-301a was decreased in TLR-triggered macrophages. Through targeting NKRF, miR-301a affected the activity of NF-κB and the expression of pro-inflammatory genes downstream of NF-κB such as COX-2, prostaglandin E2 and interleukin-6. In addition, when lipopolysaccharide-treated macrophages were simultaneously stimulated with trichostatin A, an inhibitor of histone deacetylases, the expression of miR-301a increased, whereas NKRF and pro-inflammatory cytokine expression decreased. However, further investigation revealed that there was no correlation between the induction of miR-301a and the inhibitory effect of trichostatin A on lipopolysaccharide-induced gene expression in macrophages. In summary, our study indicates a new mechanism by which miR-301a regulates inflammatory cytokine expression in macrophages, which may clarify the regulatory role of micro RNAs in immune-mediated inflammatory responses. [ABSTRACT FROM AUTHOR]

A sensitive liquid chromatographic-tandem mass spectrometry(LC-MS[sol ]MS) method was developed for the determination of rizatriptan in human plasma. The analytes were extracted from plasma samples by liquid-liquid extraction, separated on a Zorbax XDB C8 column (150 × 4.6 mm i.d.) and detected by tandem mass spectrometry with an electrospray ionization interface. Zomitriptan was used as the internal standard. The method had a lower limit of quantitation of 50 pg[sol ]mL for rizatriptan, which showed more sensitivity and speed of analysis compared with reported methods. The within- and between-day precision was measured to be below 11.71% and accuracy between −5.87 and 0.86% for all quality control samples. This quantitation method was successfully applied to the evaluation of the pharmacokinetic profiles of rizatriptan after single oral administration of 5, 10 and 15 mg rizatriptan tablets to 10 healthy volunteers (five males and five females). Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This report compares the efficacy of timolol maleate 0.5% eyedrops ( TM) with that of timolol maleate 0.5% ophthalmic gel-forming solution in the treatment of infantile hemangiomas ( IHs). Sixty-six patients undergoing treatment with topical timolol were retrospectively reviewed; our results revealed similar therapeutic efficacies for both types of timolol formulations. Early treatment initiation (<3 mos) and superficial lesions correlated with better treatment response. TM eyedrops may be a more cost effective, equally efficacious modality of treatment for IHs. [ABSTRACT FROM AUTHOR]

The article presents chemical equations for the article "An Asymmetric Approach to Bicyclo[2.2.1]heptane-1-carboxylates via a Formal [4 + 2] Cycloaddition Reaction Enabled by Organocatalysis" by J. G. Fu and others published in "Organic and Biomolecular Chemistry" in 2016.

An abstract of the article "A 10-Year Review of Cutaneous Nontuberculous Mycobacterium in Asian Children," by Shanna Shan-Yi Ng and colleagues is presented.

Purpose: This study aimed to explore the utility of hippocampal radiomics using multiparametric simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) for early diagnosis of Alzheimer's disease (AD)., Methods: A total of 53 healthy control (HC) participants, 55 patients with amnestic mild cognitive impairment (aMCI), and 51 patients with AD were included in this study. All participants accepted simultaneous PET/MRI scans, including 18 F-fluorodeoxyglucose ( 18 F-FDG) PET, 3D arterial spin labeling (ASL), and high-resolution T1-weighted imaging (3D T1WI). Radiomics features were extracted from the hippocampus region on those three modal images. Logistic regression models were trained to classify AD and HC, AD and aMCI, aMCI and HC respectively. The diagnostic performance and radiomics score (Rad-Score) of logistic regression models were evaluated from 5-fold cross-validation., Results: The hippocampal radiomics features demonstrated favorable diagnostic performance, with the multimodal classifier outperforming the single-modal classifier in the binary classification of HC, aMCI, and AD. Using the multimodal classifier, we achieved an area under the receiver operating characteristic curve (AUC) of 0.98 and accuracy of 96.7% for classifying AD from HC, and an AUC of 0.86 and accuracy of 80.6% for classifying aMCI from HC. The value of Rad-Score differed significantly between the AD and HC (p < 0.001), aMCI and HC (p < 0.001) groups. Decision curve analysis showed superior clinical benefits of multimodal classifiers compared to neuropsychological tests., Conclusion: Multiparametric hippocampal radiomics using PET/MRI aids in the identification of early AD, and may provide a potential biomarker for clinical applications., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)