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Aloperine (ALO), a quinolizidine‐type alkaloid isolated from a natural Chinese herb, has shown promising antitumor effects. Nevertheless, its common mechanism of action and specific target remain elusive. Here, it is demonstrated that ALO inhibits the proliferation and migration of non‐small cell lung cancer cell lines in vitro and the tumor development in several mouse tumor models in vivo. Mechanistically, ALO inhibits the fusion of autophagosomes with lysosomes and the autophagic flux, leading to the accumulation of sequestosome‐1 (SQSTM1) and production of reactive oxygen species (ROS), thereby inducing tumor cell apoptosis and preventing tumor growth. Knockdown of SQSTM1 in cells inhibits ROS production and reverses ALO‐induced cell apoptosis. Furthermore, VPS4A is identified as a direct target of ALO, and the amino acids F153 and D263 of VPS4A are confirmed as the binding sites for ALO. Knockout of VPS4A in H1299 cells demonstrates a similar biological effect as ALO treatment. Additionally, ALO enhances the efficacy of the anti‐PD‐L1/TGF‐β bispecific antibody in inhibiting LLC‐derived subcutaneous tumor models. Thus, ALO is first identified as a novel late‐stage autophagy inhibitor that triggers tumor cell death by targeting VPS4A. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of Alzheimer's disease (AD) was recently shifted from clinical to biological construct to reflect underlying neuropathological status, where amyloid deposition designated patients to the Alzheimer's continuum, and additional tau positivity represented AD. Objective: To investigate white matter (WM) alteration in the brain of patients in the Alzheimer's continuum. Methods: A total of 236 subjects across the clinical and biological spectra of AD were included and stratified by normal/abnormal (–/+) amyloid (A) and tau (T) status based on positron emission tomography results, yielding five groups: A–T–cognitively normal (CN), A+T–CN, A+T+ CN, A+T+ mild cognitive impairment, and A+T+ AD. WM alteration was measured by diffusion tensor imaging (DTI). Group differences, correlation of DTI measures with amyloid and tau, and diagnostic performance of such measures were evaluated. Results: Compared with A–T–CN, widespread WM alteration was observed in the Alzheimer's continuum, including hippocampal cingulum (CGH), cingulum of the cingulate gyrus, and uncinate fasciculus. Diffusion changes measured by regional mean fractional anisotropy (FA) in the bilateral CGH were first detected in the A+T+ CN group and associated with tau burden in the Alzheimer's continuum (p < 0.001). For discrimination between A+T+ CN and A–T–CN groups, CGH FA achieved accuracy, sensitivity, and specificity of 74%, 58%, and 78% for right CGH and 57%, 83%, and 47% respectively for left CGH. Conclusion: WM alteration is widespread in the Alzheimer's continuum. Diffusion alteration in CGH occurred early and was correlated with tau pathology, thus may be a promising biomarker in preclinical AD. [ABSTRACT FROM AUTHOR]

Background and Aim: Programmed death‐ligand 1 (PD‐L1) was involved in regulating Th17/Treg cell balance in ulcerative colitis (UC). Extracellular vesicles (EVs) from genetically modified bone marrow mesenchymal stem cells (BMSCs) can serve as a stable delivery system to overexpress PD‐L1. The study was designed to evaluate the therapeutic mechanism of BMSC‐EVs overexpressing PD‐L1 (PD‐L1‐EVs) on ulcerative colitis. Methods: Experimental model of UC was established in rats by drinking 5% dextran sulfate sodium (DSS). Apoptosis‐related proteins, inflammatory response‐related factors and oxidative stress related mediators were detected. Westernblot was used to detecte key proteins in the PI3K/AKT signaling pathway and its downstream effectors. The CD4+Foxp3+Treg cells and CD4+IL‐17A+Th17 cells in spleen and mesenteric lymph nodes (MLNs) was detected by flow cytometry. Results: PD‐L1‐EVs significantly alleviated the manifestations and pathological damage of UC rats by inhibiting the expression of IFN‐γ, IL‐1β, IL‐8, IL‐6, IL‐2, BAX, NF‐κB, TNF‐α, MPO, and MDA, and up‐regulating the expression of IL‐4, BCL‐2, SOD, and GSH. Furthermore, the proportions of Th17 cells were decreased and that of Treg cells were upregulated by PD‐L1‐EVs treatment. PTEN inhibitors (bpv) partially abolished the inhibitory effect of PD‐L1‐EVs on PI3K‐AKT signaling and impaired the therapeutic efficacy of PD‐L1‐EVs. Conclusions: PD‐L1‐EVs mitigated colonal inflammation, apoptosis and oxidative stress through blocking the activation of PI3K/Akt/mTOR pathway and regulating the balance of Th17/Treg cells. [ABSTRACT FROM AUTHOR]

Background: The physical process of axial length growth among children and its role in the occurrence of myopia remain insufficiently explored. In this study, we investigate the patterns of ocular axial growth among persistent myopia (PM) and persistent non-myopia (PNM) children aged 3 to 15 years. Methods: A group of 6353 children aged 3 to 15 years, selected from rural schools in China, were followed up annually for 2 years. Biometric measurements including axial length (AL) and spherical equivalent refraction (SER) were obtained. Body height was recorded. Children were divided into two groups: PM group defined as SER of −0.50 D or less; PNM group defined as −0.50 D < SER < +3.0 D during follow-up. Results: Annual AL growth was fairly consistent for PNM eyes of children aged 3 to 11 years and then reduced significantly (independent t test, p < 0.001) for children aged 12 years and older. This pattern of AL changes was similar for PM children, although the AL growth was greater among them. Among children aged 6 and older, body height change was concomitant to AL growth (p < 0.01) and SER myopic shift (p < 0.001) until reaching 12 years old (p = 0.308 and p = 0.679, respectively). Conclusions: Stature growth and AL growth are both remarkable and consistent and concomitant but start to attenuate when the children reach 10 to 12 years old among emmetropic children. This observation suggests that AL growth is driven by physical development until 12 years old, whereas its excessive growth is dominated by myopia development. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) was recently defined as a biological construct to reflect neuropathologic status, and both abnormal amyloid and tau are required for a diagnosis of AD. We aimed to determine the proton MR spectroscopic (1H-MRS) patterns of the posterior cingulate in biologically defined AD. A total of 68 participants were included in this study, comprising 37 controls, 16 early AD, and 15 late AD, who were classified according to their amyloid and tau status and presence of hippocampal atrophy. Compared with controls, early AD showed lower N-acetylaspartate (NAA)/creatine (Cr) (p = 0.003), whereas late AD showed lower NAA/Cr and higher myoInositol (mI)/Cr (all with p < 0.05). Lower NAA/Cr correlated with a greater global amyloid load (r = −0.47, p < 0.001) and tau load (r = −0.51, p < 0.001) and allowed a discrimination of early AD from controls (p < 0.001). Subgroup analysis showed that NAA/Cr also allowed a differentiation of early AD from controls in the cognitively unimpaired subjects, with an area under the receiver operating characteristics curve, sensitivity, and specificity of 0.96, 100%, and 83.8%, respectively. Lower posterior cingulate NAA levels may help to inform underlying neuropathologic changes in the early stage of AD. [ABSTRACT FROM AUTHOR]

Background: Noninvasive detection of Helicobacter pylori plays an important role in clinical practice. However, few noninvasive methods have been applied in epidemiological studies due to the requirement for expensive equipment and complicated processes. The aim of this study was to establish a reliable, fast, and inexpensive noninvasive method based on CRISPR‐Cas12a technology for the detection of Helicobacter pylori in stool specimens. Method: A novel detection method based on CRISPR‐Cas12a technology was established and validated with 41 stool specimens collected from Zhujiang Hospital and compared with reliable Helicobacter pylori detection assays, such as the rapid urease test and urea breath test. Result: A CRISPR‐Cas12a system‐based method was established, and its sensitivity and specificity were evaluated. Utilizing a lateral flow biosensor, the limit of detection was 5 copies/μl, and our method could successfully distinguish Helicobacter pylori from other pathogens, suggesting no cross‐reactivity with other pathogens. Furthermore, lateral flow biosensor strips were utilized to test stool specimens, which could display the detection results in an accessible way. Conclusion: Our CRISPR‐Cas12a system‐based method successfully detected Helicobacter pylori in stool specimens. It is a rapid, simple, and inexpensive method for the detection and screening of Helicobacter pylori, which makes it a very promising supplemental test. However, its sensitivity and specificity compared with those of the gold standard test still need to be examined. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is common in multiple sclerosis (MS). However, the relationship between cognitive deficits and microstructural abnormalities in Chinese MS patients remains unclear. We aimed to investigate the importance of microstructural abnormalities and the associations with cognitive impairment in Chinese MS patients. Methods: Three‐dimensional T1‐weighted magnetic resonance imaging (MRI) scans were obtained from 36 relapsing remitting MS patients. Diffusion tensor imaging (DTI) scans were acquired for 29 (81%) patients. Cognitive impairment was assessed using a comprehensive neuropsychological battery. Patients were classified into cognitively impaired (CI) group and cognitively preserved (CP) group. Using volBrain and FSL software, we assessed white matter lesion burden, white matter (WM) and gray matter (GM) volumetric as well as microstructural diffusivity. MRI variables explaining cognitive impairment were analyzed. Results: Fifteen (42%) patients were classified as CI. Verbal learning and memory was the most commonly impaired domain (n = 16, 44%). CI patients had lower mean skeleton fractional anisotropy (FA) value than CP patients (275.45 vs. 283.61 × 10−3, P = 0.023). The final predicting model including demographic variables and global skeleton mean diffusivity (MD) explained 43.6% of variance of the presence of cognitive impairment (β = 0.131, P = 0.041). CI patients showed a widespread change of microstructural integrity comparing to CP patients, which was rarely overlapping with lesion probability map. Microstructural abnormalities in corpus callosum were associated with performance in verbal learning and memory, processing speed and selective attention (P < 0.05). Conclusion: Loss of microstructural integrity demonstrated by DTI helps explain cognitive dysfunction in Chinese MS patients. [ABSTRACT FROM AUTHOR]

Jixuepaidu Tang-1 is obtained from the decoction of the Chinese traditional medicinal plants including Centella asiatica, Astragalus membranaceus, and Sanguis draconis. Transforming growth factor-β1 (TGF-β1)/serum- and glucocorticoid-inducible kinase-1 (SGK1)-induced epithelial-mesenchymal transition (EMT) plays a pivotal role in the pathogenesis of diabetic nephropathy (DN). In addition, long non-coding RNAs (lnRNAs) participate in the development of DN, but the role of lncRNA LOC498759 in DN is still unclear. This study aims to investigate the role of Jixuepaidu Tang-1 in regulating podocyte injury and renal damage in DN and to validate whether the mechanisms involve TGF-β1/SGK1 signaling and LOC498759. The drug treatment was initiated 2 weeks after the DN modeling. The MTT method and TUNEL staining were used to measure cell viability and apoptosis, respectively. Immunofluorescence staining was used to detect the expression of nephrin and desmin in podocytes. Sera from the Jixuepaidu Tang-1-treated mice reversed the high glucose (HG)-induced podocyte injury and EMT in mouse podocytes. Further in vivo assay revealed that Jixuepaidu Tang-1 not only reduced the ratio of the kidney to body weight, 24 h-urine total protein, and blood glucose, but alleviated glomerular mesangial extracellular matrix deposition and glomerular cell apoptosis in the streptozotocin-induced DN mice. Mechanically, the mechanisms of Jixuepaidu Tang-1 may involve the suppression of EMT by inhibiting the TGF-β1/SGK1-induced LOC498759 expression. Collectively, Jixuepaidu Tang-1 attenuates podocyte injury and renal damage in DN, and inhibits EMT through suppressing TGF-β1/SGK1-LOC498759 signaling. [ABSTRACT FROM AUTHOR]

Compound sophorae decoction (CSD), a traditional Chinese medicine (TCM) formula, has been voluminously used in China to deal with ulcerative colitis and gained significant therapeutic effect. Tremendous explorations have unraveled a contributory role of inflammatory bowel disease (IBD) like ulcerative colitis (UC) and Crohn's disease (CD) at the onset of colorectal cancer, scilicet, and colitis-related cancer (CRC). In light of the anti-inflammatory properties of CSD in UC, we appraised its chemoprevention capacity and underlying mechanism in ulcerative colitis-related colorectal cancer (UCRCC), employing a model of azoxymethane (AOM) plus dextran sulfate sodium- (DSS-) induced colorectal cancer (CRC) in C57BL/6 mice. Rapturously, our results illuminated the ameliorative effect of CSD against UCRCC in mice portrayed by lesser polyps or adenomas, attenuated colonic xenograft tumor growth in company with the preferable well-being of mice in contrast to the Model Group. We examined significant downregulation of proinflammatory cytokines such as TNF-α, NF-κB, IL-6, STAT3, and IL-17 after exposure to CSD, with the concomitant repression of inflammation-associated proteins, including COX-2 and iNOS. Independent of this, treatment with CSD declined the proportion of T helper 17 cells (Th17) and protein level of matrix metallopeptidase 9 (MMP-9). Moreover, transmission electron microscopy (TEM) detected observably suppressed mitophagy in mice administered with CSD and that was paralleled by the pro-apoptotic effect as indicated by upregulating caspase-3 together with caspase-9 and deregulating B-cell lymphoma 2 (Bcl-2). In closing, these findings suggest CSD executes the UCRCC-inhibitory activity through counteracting inflammatory responses and rescuing detuning of apoptosis as well as neutralizing overactive mitophagy, concurring to build up an oncosuppressive microenvironment. [ABSTRACT FROM AUTHOR]

Background: One significant barrier to incorporate Alzheimer's disease (AD) imaging biomarkers into diagnostic criteria is the lack of standardized methods for biomarker quantification. The European Alzheimer's Disease Consortium-Alzheimer's Disease Neuroimaging Initiative (EADC-ADNI) Harmonization Protocol project provides the most authoritative guideline for hippocampal definition and has produced a manually segmented reference dataset for validation of automated methods.Purpose: To validate automated hippocampal volumetry using AccuBrain™, against the EADC-ADNI dataset, and assess its diagnostic performance for differentiating AD and normal aging in an independent cohort.Material and Methods: The EADC-ADNI reference dataset comprise of manually segmented hippocampal labels from 135 volumetric T1-weighted scans from various scanners. Dice similarity coefficient (DSC), intraclass correlation coefficient (ICC), and Pearson's r were obtained for AccuBrain™ and FreeSurfer. The magnetic resonance imaging (MRI) of a separate cohort of 299 individuals (150 normal controls, 149 with AD) were obtained from the ADNI database and processed with AccuBrain™ to assess its diagnostic accuracy. Area under the curve (AUC) for total hippocampal volumes (HV) and hippocampal fraction (HF) were determined.Results: Compared with EADC-ADNI dataset ground truths, AccuBrain™ had a mean DSC of 0.89/0.89/0.89, ICC of 0.94/0.96/0.95, and r of 0.95/0.96/0.95 for right/left/total HV. AccuBrain™ HV and HF had AUC of 0.76 and 0.80, respectively. Thresholds of ≤ 5.71 mL and ≤ 0.38% afforded 80% sensitivity for AD detection.Conclusion: AccuBrain™ provides accurate automated hippocampus segmentation in accordance with the EADC-ADNI standard, with great potential value in assisting clinical diagnosis of AD. [ABSTRACT FROM AUTHOR]

Background: Structural connectivity assessed by diffusion tensor imaging (DTI) is reportedly associated with tau pathology in Alzheimer's disease. In this study, we aimed to determine whether structural connectivity derived from DTI can reveal tau positivity at the individual level by utilizing a machine learning classifier. Method: All data were collected from Alzheimer's Disease Neuroimaging Initiative Phase 3. Sixty subjects (27 females; age range, 56‐94 years old) who underwent tau positron emission tomography (PET) and DTI scans at baseline were included. Tau pathology was assessed by 18F‐Flortaucipir standardized uptake value ratio PET in Braak stage composite regions. The cutoff point denoting positivity was set at 1.23 (Jack et al. 2017), yielding 30 scans each for normal and abnormal scans. DTI scans were acquired with 6 b0 and 48 diffusion‐weighted volumes with b = 1000 s/mm2 at 2.7 × 2.7 × 2.7 mm3 resolution and corrected for head motion and eddy‐current‐induced artifacts. Whole‐brain white‐matter fiber was tracked by deterministic tractography using DSI Studio under Q‐space diffeomorphic reconstruction scheme. The brain was parcellated into 120 regions‐of‐interest (ROIs) based on Automated Anatomical Labeling atlas 2, and each ROI served as a node of the network. Pairwise connectivity strength was quantified by the number of tracts connecting two ROIs and populated as a 120 × 120 connectivity matrix, serving as features for the following classification. A support vector machine classifier with the radial basis function kernel was trained for classification with stratified 10‐fold cross‐validation. Performance was evaluated by accuracy, sensitivity, and specificity. Result: The average classification accuracy, sensitivity, and specificity were achieved at 65.0%, 86.7%, and 23.2% respectively. Conclusion: Structural connectivity achieved high sensitivity in the detection of tau positivity, but it may not enable accurate classification at the individual level. [ABSTRACT FROM AUTHOR]

Importance: Myopia has reached epidemic levels in parts of East and Southeast Asia. However, there is no effective intervention to prevent the development of myopia.Objective: To assess the efficacy of increasing time spent outdoors at school in preventing incident myopia.Design, Setting, and Participants: Cluster randomized trial of children in grade 1 from 12 primary schools in Guangzhou, China, conducted between October 2010 and October 2013.Interventions: For 6 intervention schools (n = 952 students), 1 additional 40-minute class of outdoor activities was added to each school day, and parents were encouraged to engage their children in outdoor activities after school hours, especially during weekends and holidays. Children and parents in the 6 control schools (n = 951 students) continued their usual pattern of activity.Main Outcomes and Measures: The primary outcome measure was the 3-year cumulative incidence rate of myopia (defined using the Refractive Error Study in Children spherical equivalent refractive error standard of ≤-0.5 diopters [D]) among the students without established myopia at baseline. Secondary outcome measures were changes in spherical equivalent refraction and axial length among all students, analyzed using mixed linear models and intention-to-treat principles. Data from the right eyes were used for the analysis.Results: There were 952 children in the intervention group and 951 in the control group with a mean (SD) age of 6.6 (0.34) years. The cumulative incidence rate of myopia was 30.4% in the intervention group (259 incident cases among 853 eligible participants) and 39.5% (287 incident cases among 726 eligible participants) in the control group (difference of -9.1% [95% CI, -14.1% to -4.1%]; P < .001). There was also a significant difference in the 3-year change in spherical equivalent refraction for the intervention group (-1.42 D) compared with the control group (-1.59 D) (difference of 0.17 D [95% CI, 0.01 to 0.33 D]; P = .04). Elongation of axial length was not significantly different between the intervention group (0.95 mm) and the control group (0.98 mm) (difference of -0.03 mm [95% CI, -0.07 to 0.003 mm]; P = .07).Conclusions and Relevance: Among 6-year-old children in Guangzhou, China, the addition of 40 minutes of outdoor activity at school compared with usual activity resulted in a reduced incidence rate of myopia over the next 3 years. Further studies are needed to assess long-term follow-up of these children and the generalizability of these findings.Trial Registration: clinicaltrials.gov Identifier: NCT00848900. [ABSTRACT FROM AUTHOR]

Purpose: Disordered sleep and myopia are increasingly prevalent among Chinese children. Similar pathways may be involved in regulation of both sleep cycles and eye growth. We therefore sought to examine the association between disordered sleep and myopia in this group. Methods: Urban primary school children participating in a clinical trial on myopia and outdoor activity underwent automated cycloplegic refraction with subjective refinement. Parents answered questions about children's sleep duration, sleep disorders (Children's Sleep Habits Questionnaire [CSHQ]), near work and time spent outdoors. Results: Among 1970 children, 1902 (96.5%, mean [standard deviation SD] age 9.80 [0.44] years, 53.1% boys) completed refraction and questionnaires. Myopia < = -0.50 Diopters was present in both eyes of 588 (30.9%) children (1329/3804 = 34.9% of eyes) and 1129 children (59.4%) had abnormal CSHQ scores (> 41). In logistic regression models by eye, odds of myopia < = -0.50D increased with worse CSHQ score (Odds Ratio [OR] 1.01 per point, 95% Confidence Interval [CI] [1.001, 1.02], P = 0.014) and more night-time sleep (OR 1.02, 95% CI [1.01, 1.04, P = 0.002], while male sex (OR 0.82, 95% CI [0.70, 0.95], P = 0.008) and time outdoors (OR = 0.97, 95% CI [0.95, 0.99], P = 0.011) were associated with less myopia. The association between sleep duration and myopia was not significant (p = 0.199) for total (night + midday) sleep. Conclusions: Myopia and disordered sleep were both common in this cohort, but we did not find consistent evidence for an association between the two. Trial Registration: clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Purpose: To identify the specific characteristics making glasses designs, particularly those compatible with adjustable glasses, more or less appealing to Chinese children and their parents. Patients and Methods: Primary and secondary school children from urban and rural China with < = −1.00 diopters of bilateral myopia and their parents ranked four conventional-style frames identified by local optical shops as popular versus four child-specific frames compatible with adjustable spectacles. Scores based on the proportion of maximum possible ranking were computed for each style. Selected children and their parents also participated in Focus Groups (FGs) discussing spectacle design preference. Recordings were transcribed and coded by two independents reviewers using NVivo software. Results: Among 136 urban primary school children (age range 9–11 years), 290 rural secondary school children (11–17 years) and 16 parents, all adjustable-style frames (scores on 0–100 scale 25.7–62.4) were ranked behind all conventional frames (63.0–87.5). For eight FGs including 12 primary children, 26 secondary children and 16 parents, average kappa values for NVivo coding were 0.81 (students) and 0.70 (parents). All groups agreed that the key changes to make adjustable designs more attractive were altering the round lenses to rectangular or oval shapes and adding curved earpieces for more stable wear. The thick frames of the adjustable designs were considered stylish, and children indicated they would wear them if the lens shape were modified. Conclusions: Current adjustable lens designs are unattractive to Chinese children and their parents, though this study identified specific modifications which would make them more appealing. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate reasons for non-compliance with post-cataract surgical follow-up in rural China, and assess the impact of incentives on improving compliance. Methods: Patients having undergone cataract surgery more than 3 months previously at cataract surgery training hospitals in Guangdong were invited by telephone and advertisements to a hospital-based study examination, with compensation for travel costs (US$$7). Information on prior post-surgical follow up was collected by questionnaire at the hospital or by telephone. Logistic regression was used to assess predictors of post-operative attendance with or without compensation. Results: Among 518 eligible patients, 426 (82.2%) underwent interviews and 342 (66.0%) attended the compensated study examination. Ninety nine participants (23.2%) reported previously returning for uncompensated follow-up ≥ 3 months post-operatively, and 225 (52.8%) had returned for any prior post-operative examination. Uncompensated follow-up at ≥ 3 months was associated with higher income ( P == 0.037), and recalling instruction by a doctor to follow-up ( P == 0.001), while age, gender, travel cost, and post-operative satisfaction and vision were not associated. Younger ( P == 0.002) patients and those reporting being instructed to follow up ( P == 0.008) were more likely to return for the compensated research examination. Among all interviewed subjects, only 170 (39.9%) reported knowing they were to return to hospital. Conclusions: Modest compensation, advertisements and telephone contact can increase medium-term follow-up rates after cataract surgery by three-fold. Better communication of specific targets for follow-up may improve follow-up compliance. [ABSTRACT FROM AUTHOR]

In this study, a particle-tracking image pyrometer (PTIP) system, based on a high-resolution high-speed camera and a digital single lens reflex (SLR) camera, was proposed to investigate the ignition characteristics of pulverized coal particles. The goal of the PTIP system was to obtain reliable simultaneous measurements of the velocity, diameter, and temperature of individual burning particles. A modified particle-tracking velocimetry (PTV) algorithm was developed to collect the image sequences of individual particles, and it could weed out defocused particles and other odd particles by low-frequency filtration. Moreover, a template matching method was adopted to distinguish particles undergoing different combustion states (homogeneous volatile combustion or heterogeneous coal/char combustion). The experimental validation was carried out under an O 2 /CO 2 atmosphere in an optically accessible flat flame-supported entrained flow reactor. Particles of Shenhua (SH) bituminous coal, in the size range of 70–133 μm, were combusted in the flue gas with gas temperature of 1400 K and O 2 concentration of 20%. The diameter-temperature patterns of particles along their trajectories were discussed. Several criteria based on statistical analysis were adopted to divide the combustion process and obtain the ignition delay time (IDT) and devolatilization duration time (DDT). • Speed, diameter and temperature of a burning particle are measured simultaneously. • Modified PTV method is used to capture the combustion sequence of single particle. • Different stages of particle combustion are distinguished by particle templates. • Statistical analysis is adopted to obtain characteristic time for combustion. • Combination of micro and macro photography improves the credibility of diagnosis. [ABSTRACT FROM AUTHOR]

Pressurized oxy-fuel combustion technology is the second generation of oxy-fuel combustion technology and has low energy consumption and low cost. In this research, a visual pressurized flat-flame reaction system was designed. A particle-tracking image pyrometer (PTIP) system based on a high-speed camera and an SLR camera was proposed. Combining the experimental system and data-processing method developed, the ignition and combustion characteristics of a single coal particle between 69 and 133 μm in size were investigated. The results indicated that at atmospheric pressure, the ignition delay time of ShanXi (SX) anthracite coal was longer than that of ShenHua (SH) bituminous coal, while that of PRB sub-bituminous coal was the shortest. As the pressure rose, the ignition delay time of the PRB sub-bituminous coal and SX anthracite coal showed a continuous increasing trend, while the ignition delay time of SH bituminous coal showed a trend of first increasing and then decreasing. Moreover, pressure also affects the pyrolysis process of coal. As the pressure increases, it became more difficult to release the volatiles produced by coal pyrolysis, which reduced the release rate of volatiles during the ignition stage, and prolonged the release time and burning duration time of volatiles. [ABSTRACT FROM AUTHOR]

Background: Structural connectivity derived from diffusion tensor imaging (DTI) reflects white matter network changes during Alzheimer's Disease (AD) progression, which can potentially serve as a biomarker for prediction. In this study we explored the ability of structural connectivity to predict mild cognitive impairment (MCI) by implementing a convolutional neural network (CNN). Method: 613 DTI scans (194 controls, 291 MCI and 128 AD) from 206 patients (113 male, 93 female; age range: 55‐91 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) Phase GO and 2 were included in this study. The clinical diagnosis at last ADNI follow‐up visit served as reference for prediction (average: 44.4 ± 26.7 months). DTI scans were acquired with 5 b0 and 41 diffusion weighted volumes with b=1000 s/mm2 at 2.7×2.7×2.7mm3 resolution. Preprocessing included eddy current correction and co‐registration to normalized T1‐weighted scans. Whole brain white matter fiber was tracked by deterministic tractography using DSI Studio under Q‐space diffeomorphic reconstruction scheme, which calculates the quantitative anisotropy mapping prior to normalization to standard space. An Automated Anatomical Labeling atlas 2 with 120 region‐of‐interests (ROI) was used to parcellate the brain, where each ROI represented a node of the network. The weight of the edge was calculated by number of tracts connecting two ROIs and normalized by medial length. Therefore a 120×120 structural connectivity matrix was generated for each scan. 80% of data was used for training and 10% of data for validation. The parameters that achieved highest accuracy on validation set was applied to the remaining 10% (hold‐out test set) for final evaluation. A seven‐layer CNN model was constructed for differentiating three groups. The performance was evaluated by accuracy and sensitivity. Result: On an average of 3.7 years before the diagnosis, the prediction accuracy was 86.9% in validation set and 85.7% in hold‐out test set. The sensitivity to predict controls and MCI were 95.0% and 93.3%, respectively. Conclusion: Using CNN, structural connectivity allowed good ability to predict MCI from cohorts at an early stage before diagnosis. [ABSTRACT FROM AUTHOR]

Background: Diffusion tensor imaging (DTI) detects white matter microstructural changes in early Alzheimer's Disease (AD), and can potentially serve as a sensitive biomarker in longitudinal scans. In this study we determined the reliability of DTI‐derived fractional anisotropy (FA) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, which to our knowledge has not been reported. Method: We selected 21 healthy subjects (12 women and 9 men; age range, 60‐89 years) from the ADNI2 with two sets of DTI performed within 3 months serving as surrogate test‐retest datasets. The subjects' cognitive status remained stable within one year. The MRI was performed on the same 3.0 T GE scanner following ADNI standard protocol for DTI acquisition (2.7×2.7×2.7 mm3, b=1000 s/mm2, 5 b0 and 41 diffusion weighted volumes). FMRIB Software Library (FSL) was used to process the DTI data to derive the FA scalar map. The two FA maps of the same subject were first co‐registered and then aligned to the JHU DTI atlas by using both linear and non‐linear registration method. A pre‐defined white matter region‐of‐interest (ROI) on the atlas was applied to the registered FA map to derive the value. The ROI related to AD were selected for analysis and included the corpus callosum (body, genu, splenium), corticospinal tract, superior longitudinal fasciculus, fronto‐occipital fasciculus and cingulum (cingulate gyrus, hippocampus). Reliability was assessed using intraclass correlation coefficient (ICC) and coefficient of variation (CoV) of the mean value within the ROI. Result: Mean ICC of the paired FA values for all ROIs were 0.97(range: 0.93‐0.99). The CoVs for selected ROIs were all within 8% and the median was all below 2%. The greatest variation was found in the right cingulum hippocampus with CoV of 2.03%, while smallest variation 0.89% was present in the left superior longitudinal fasciculus. No significant correlation was found between ICC and CoV. Conclusion: Using short interval longitudinal scans of healthy subjects in the ADNI dataset as surrogate test‐retest datasets, we found FA values of DTI exhibited good reliability. Our results lay the foundation for our future analysis of longitudinal DTI datasets in the ADNI database. [ABSTRACT FROM AUTHOR]

Rainfall gauges are always sparse in the arid and semi-arid areas of Northwest China, which makes it difficult to precisely study the characteristics of drought at a large scale in this region and similar areas. This study used the TRMM (The Tropical Rainfall Measuring Mission) multi-satellite precipitation data to study the spatial-temporal evolution of drought in the Loess Plateau based on the SPI (Standardized Precipitation Index) drought index for the period of 1998–2014. The results indicate that the monthly TRMM precipitation data are well matched with the observed precipitation, indicating that this remotely sensed data set can be reliably used to calculate the SPI drought index. Based on the study findings, the average precipitation in the Loess Plateau is showing a significant increasing trend at the rate of 4.46 mm/year. From the spatial perspective, the average annual precipitation in the Southeast is generally greater than that in the Northwest. However, the annual precipitation in the Southeast area is showing a decreasing trend, whereas, the annual precipitation in the northwest areas is showing an increasing trend. Through the SPI analysis, the 3-month SPI and 12-month SPI were both showing an increasing trend, which indicates that the drought severity in the Loess Plateau was a generally declining trend at a seasonal to annual time scale. From the spatial perspective, the SPI values in the Central and Northwest of the Loess Plateau were significantly increasing, whereas, the SPI values in the southern area of the Loess Plateau were slightly decreasing. From the seasonal characteristics, the high-risk area for drought in the spring was concentrated in the northeast and southwest part, and in the summer and autumn, the high-risk area was transferred to the south part. Through this study, it is concluded that the Loess Plateau was likely getting wetter during the time period since the Grain-for-Green Project (1999–2012) was implemented, which replaced much farmland with forestry. This is a positive signal for vegetation recovery and ecological restoration in the near future. [ABSTRACT FROM AUTHOR]

Abstract Accumulating evidence indicates that microRNA-146a (miR-146a), a well-known anti-inflammatory miRNA, acts as a negative feedback regulator of the innate immune response, but its role in modulation of inflammatory bowel disease (IBD) remains unclear and the issue related to the stability of exogenous miR-146a in blood is up in the air. In this study, extracellular vesicles (EVs) from cultured medium of bone-marrow mesenchymal stem cells (BMSCs) transfected with recombinant lentiviruses can serve as a stable delivery system and overexpress miR-146a, which significantly inhibited TNF receptor–associated factor 6 (TRAF6) and IL-1 receptor-associated kinase 1 (IRAK1) expression in TNBS-induced colitis of rats. Moreover, the increased phosphorylation levels of NF-κB p65 and IκBα were down-regulated by the administration of EVs containing miR-146a. Coupled with the associated influence of over-expressed miR-146a on phosphorylated proteins above, the production of inflammation factors such as tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and Interleukin-1β is apparently suppressed by this non-coding RNA. Collectively, these data elucidated that EVs containing miR-146a ameliorates experimental colitis caused 2,4,6‑trinitrobenzenesulfonic acid (TNBS) by targeting TRAF6 and IRAK1. Highlights • Extracellular vesicles can be used as a stable delivery system transporting miR-146a. • MiR-146a significantly inhibited TRAF6 and IRAK1 expression. • The increased phosphorylation levels of NF-κB p65 and IκBα were hampered by miR-146a. • MiR-146a suppressed TNF-α, IL-6 and IL-1β production induced by TNBS. [ABSTRACT FROM AUTHOR]

Abstract Th17 cells play an important role in the immune imbalance and inflammatory state in colonic mucosa of Inflammatory Bowel Disease (IBD) and to clarify the mechanism that affect the differentiation of Th17 cells will help us find a new target for the treatment of IBD. MiR-155 which is reported to have an important role in regulating immune system function is also detected to be significantly up-regulated in colonic tissues of IBD patients. However, whether and how miR-155 affects the differentiation of Th17 cells in the colon of IBD patients is still worth studying. Here, we investigated the role of miR-155 in TNBS-induced rat colitis. Firstly, we found that the disease activity index (DAI) and Colon pathological changes were significantly reduced (P < 0.05) by using miR-155 inhibition sequences delivered by lentiviral vector, which revealed that miR-155 inhibition ameliorated TNBS-Induced experimental colitis. Then, we carried out flow cytometry, ELISA, qRT-PCR, and found that in TNBS+miR-155 inhibition group, the proportion of Th17 cells in spleens and mesenteric lymph nodes (MLNs) and the level of the Th17 cell-associated cytokines IL-6, IL-17A, IL-17F and IL-21 in colon tissues were significantly reduced (P < 0.05), which revealed that miR-155 inhibition regulated the differentiation and function of Th17 cells. Finally, we discovered that Jarid2 was significantly elevated (P < 0.05) by miR-155 inhibition and notch1 expression was inversely correlated with Jarid2 by using Immunohistochemistry and western blot. This study suggests that miR-155 inhibition ameliorates TNBS-induced colitis by regulating the Th17 cells differentiation and function and Jarid2/notch1 is closely related with the process. Highlights • miR-155 inhibition could ameliorate TNBS-Induced experimental acute colitis in rat. • miR-155 inhibition reduced the differentiation and function of Th17 cells. • miR-155 inhibition up regulates the expression of Jarid2. • Jarid2 and notch1 expression was negatively correlated in TNBS-Induced experimental acute colitis. • Jarid2/notch1 is closely related with the process that miR-155 inhibition regulates the differentiation and function of Th17 cells. [ABSTRACT FROM AUTHOR]

Our study was to explore the potential role of miRNA-200b in modulating tumorigenesis in the model of ulcerative colitis-related colorectal cancer (UCRCC) and, further, to decipher the underlying mechanisms associated with this effect. In this study, we examined a greater number of polyps or adenomas, a higher grade of epithelial dysplasia accompanied with a decrease in survival ratio in azoxymethane (AOM)/dextran sulfate sodium (DSS) model mice compared to mice treated with over-expressed miRNA-200b. Surprisingly, enforced miRNA-200b expression significantly suppressed AOM/DSS-induced up-regulation of oncologic markers including β-catenin and CD133. Independent of this, treatment with miRNA-200b obviously attenuated inflammatory responses, as indicated by down-regulating tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β) and blockade of AKT2-mediated NF-κB/IL-6/STAT3 signaling pathway. Furthermore, a simultaneous shift in epithelial-mesenchymal transition (EMT) markers such as E-cadherin and N-cadherin were observed to be increased and decreased, respectively. Coupled with the associated influence of over-expressed miRNA-200b were change in colorectal cell morphology shown by Transmission electron microscope (TEM) and a decrease in expression of rho-kinase2 (ROCK2) together with AKT2 phosphorylation (p-AKT2). Moreover, mice which were transfected with negative control of miRNA-200b possessed results that were in line with that obtained from AOM/DSS model mice. Additionally, we demonstrated that the 3′untranslated region (UTR) of AKT2 was a direct target of miRNA-200b through bioinformatics analysis and dual-luciferase assay. Collectively, these findings suggest that miRNA-200b's contribution to tumor-suppressing program was correlated with EMT and inflammatory responses in a AKT2-dependent manner. [ABSTRACT FROM AUTHOR]

Bone marrow-derived mesenchymal stem cells (BMSCs) hold great promise for the treatment of inflammatory bowel disease owing to their immunosuppressive property and tissue healing potential. The balance between regulatory T cells (Tregs) and T helper (Th)17 cells plays a crucial role in BMSC-mediated immunosuppression. Interleukin (IL)-35 is a newly identified anti-inflammatory cytokine required for the expansion of Tregs and suppression of Th17 cell differentiation. IL-35 can amplify the immunosuppressive property of BMSCs when overexpressed in these cells. However, the reparative capability of BMSCs in vivo is limited, partly due to the poor homing efficiency of BMSCs to inflamed colons. Up-regulation of CXC chemokine receptor 4 (CXCR4) expression in BMSCs may affect the directional homing of implanted BMSCs via stromal-derived factor-1. In this study, by lentivirus-mediated introduction of CXCR4 and IL-35 genes to modify rat BMSCs, we observed enhanced migration and strengthened immunomodulatory activities of the genetically engineering BMSCs. These results suggest that modification of BMSCs by dual expression of CXCR4 and IL-35 may provide an effective therapeutic strategy for inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play an important role in regulating immune system function by mRNA destabilisation or inhibition of translation. Recently, miR-155 was detected to be significantly up-regulated in colonic tissues of patients with active UC. However, it is unknown whether miR-155 is involved in the pathogenesis of UC and how it influences immune response in dextran sulfate sodium (DSS)-induced colitis mice. Here, we investigated the role of miR-155 in UC. Firstly, through bioinformatics analysis and luciferase report assay, we found Jarid2 was a direct target of miR-155; then, we carried out in situ hybridization, immunofluorescence and flow cytometry, and revealed that miR-155 levels were increased, Jarid2 levels were decreased and the frequency of Th17 cells was elevated in DSS-induced mice; we also used lentiviral vector to deliver miR-155 inhibition sequences to silence miR-155 that was effectively taken up by epithelial cells. MiR-155 inhibition attenuated DSS-induced colonic damage and inhibited Th17 cells differentiation. This study suggests that miR-155 plays a host-damaging role during DSS-induced colitis mice and induces Th17 differentiation by targeting Jarid2. [ABSTRACT FROM AUTHOR]

Objective To determine longitudinal changes in angle configuration in the eyes of primary angle-closure suspects (PACS) treated by laser peripheral iridotomy (LPI) and in untreated fellow eyes. Design Longitudinal cohort study. Participants Primary angle-closure suspects aged 50 to 70 years were enrolled in a randomized, controlled clinical trial. Methods Each participant was treated by LPI in 1 randomly selected eye, with the fellow eye serving as a control. Angle width was assessed in a masked fashion using gonioscopy and anterior segment optical coherence tomography (AS-OCT) before and at 2 weeks, 6 months, and 18 months after LPI. Main Outcome Measures Angle width in degrees was calculated from Shaffer grades assessed under static gonioscopy. Angle configuration was also evaluated using angle opening distance (AOD250, AOD500, AOD750), trabecular-iris space area (TISA500, TISA750), and angle recess area (ARA) measured in AS-OCT images. Results No significant difference was found in baseline measures of angle configuration between treated and untreated eyes. At 2 weeks after LPI, the drainage angle on gonioscopy widened from a mean of 13.5° at baseline to a mean of 25.7° in treated eyes, which was also confirmed by significant increases in all AS-OCT angle width measures ( P <0.001 for all variables). Between 2 weeks and 18 months after LPI, a significant decrease in angle width was observed over time in treated eyes ( P <0.001 for all variables), although the change over the first 5.5 months was not statistically significant for angle width measured under gonioscopy ( P = 0.18), AOD250 ( P = 0.167) and ARA ( P = 0.83). In untreated eyes, angle width consistently decreased across all follow-up visits after LPI, with a more rapid longitudinal decrease compared with treated eyes ( P values for all variables ≤0.003). The annual rate of change in angle width was equivalent to 1.2°/year (95% confidence interval [CI], 0.8–1.6) in treated eyes and 1.6°/year (95% CI, 1.3–2.0) in untreated eyes ( P <0.001). Conclusions Angle width of treated eyes increased markedly after LPI, remained stable for 6 months, and then decreased significantly by 18 months after LPI. Untreated eyes experienced a more consistent and rapid decrease in angle width over the same time period. [ABSTRACT FROM AUTHOR]