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Fulltext 1H NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease

Xu J, Jiang H, Li J, Cheng KK, Dong J, Chen Z

PLoS One, 2015;10(4):e0119654.
PMID: 25849323 DOI: 10.1371/journal.pone.0119654

Wilson's disease (WD), also known as hepatoleticular degeneration (HLD), is a rare autosomal recessive genetic disorder of copper metabolism, which causes copper to accumulate in body tissues. In this study, rats fed with copper-laden diet are used to render the clinical manifestations of WD, and their copper toxicity-induced organ lesions are studied. To investigate metabolic behaviors of 'decoppering' process, penicillamine (PA) was used for treating copper-laden rats as this chelating agent could eliminate excess copper through the urine. To date, there has been limited metabolomics study on WD, while metabolic impacts of copper accumulation and PA administration have yet to be established.
Fulltext The pandemic and changes in early career researchers' career prospects, research and publishing practices

Jamali HR, Nicholas D, Sims D, Watkinson A, Herman E, Boukacem-Zeghmouri C, et al.

PLoS One, 2023;18(2):e0281058.
PMID: 36791119 DOI: 10.1371/journal.pone.0281058

INTRODUCTION: As part of the Harbnger-2 project, this study aimed to discover the impact of the COVID-19 pandemic on junior researchers' work-life, career prospects, research and publishing practices and networking.
METHODS: An online international survey of 800 early career researchers (ECRs) was conducted in 2022. A questionnaire was developed based on three rounds of interviews and distributed using multiple channels including publishers, social media, and direct email to ECRs.
RESULTS: The impact of the pandemic on career prospects, morale, job security, productivity, ability to network and collaborate, and quality and speed of peer review has on the whole been more negative than positive. A quarter of ECRs shifted their research focus to pandemic-related topics and half of those who did, benefited largely due to increased productivity and impact. The majority worked remotely/from home and more than two-thirds of those who did so benefitted from it. While virtual or hybrid conferences have been embraced by the majority of ECRs, around a third still preferred face-to-face only conferences. The use of library online platforms, Sci-Hub, ResearchGate, Google Scholar and smartphone to search and access full-text papers increased. ECRs prioritised journals with fast submission procedures for the publishing of their papers and spent more time on increasing the visibility of their research. Fees were a problem for publishing open access.
CONCLUSION: Although, generally, the pandemic negatively impacted many aspects of ECRs' work-life, certain research areas and individuals benefited from being more appreciated and valued, and, in some cases, resulted in increased resources, better productivity and greater impact. Changes, such as the use of digital technologies and remote working created new opportunities for some ECRs. While continuing work flexibility and hybrid conferences might benefit some ECRs, institutions should also take measures to help those ECRs whose career and productivity have been adversely impacted.
Fulltext The communication of artificial intelligence and deep learning in computer tomography image recognition of epidemic pulmonary infectious diseases

Wang W, Zhao X, Jia Y, Xu J

PLoS One, 2024;19(2):e0297578.
PMID: 38319912 DOI: 10.1371/journal.pone.0297578

The objectives are to improve the diagnostic efficiency and accuracy of epidemic pulmonary infectious diseases and to study the application of artificial intelligence (AI) in pulmonary infectious disease diagnosis and public health management. The computer tomography (CT) images of 200 patients with pulmonary infectious disease are collected and input into the AI-assisted diagnosis software based on the deep learning (DL) model, "UAI, pulmonary infectious disease intelligent auxiliary analysis system", for lesion detection. By analyzing the principles of convolutional neural networks (CNN) in deep learning (DL), the study selects the AlexNet model for the recognition and classification of pulmonary infection CT images. The software automatically detects the pneumonia lesions, marks them in batches, and calculates the lesion volume. The result shows that the CT manifestations of the patients are mainly involved in multiple lobes and density, the most common shadow is the ground-glass opacity. The detection rate of the manual method is 95.30%, the misdetection rate is 0.20% and missed diagnosis rate is 4.50%; the detection rate of the DL-based AI-assisted lesion method is 99.76%, the misdetection rate is 0.08%, and the missed diagnosis rate is 0.08%. Therefore, the proposed model can effectively identify pulmonary infectious disease lesions and provide relevant data information to objectively diagnose pulmonary infectious disease and manage public health.
Fulltext Exploring the determinants of users' co-creation behavior on music streaming platforms in China

Xu J, Gong J, Ji D

PLoS One, 2023;18(12):e0291313.
PMID: 38150464 DOI: 10.1371/journal.pone.0291313

Music streaming platforms have recently become one of the latest innovative music devices used to replace traditional music sets. In order to examine users' behavior on music streaming platforms, this study proposes an extended research model based on flow theory and investigates the relationship between flow experience and co-creation behavior. A partial least square methodology was employed to test the proposed model and corresponding hypotheses on data collected from 390 survey samples. The results showed that flow experience has a significant influence on users' co-creation behavior. Among the three antecedents, only perceived skill and perceived interactivity have the strongest effects on flow experience, while perceived control has little effect on flow experience. This study discusses some valuable theoretical implications and offers insights useful for both researchers and practitioners.
Fulltext NMR-based metabolomics Reveals Alterations of Electro-acupuncture Stimulations on Chronic Atrophic Gastritis Rats

Xu J, Zheng X, Cheng KK, Chang X, Shen G, Liu M, et al.

Sci Rep, 2017 03 30;7:45580.
PMID: 28358020 DOI: 10.1038/srep45580

Chronic atrophic gastritis (CAG) is a common gastrointestinal disease which has been considered as precancerous lesions of gastric carcinoma. Previously, electro-acupuncture stimulation has been shown to be effective in ameliorating symptoms of CAG. However the underlying mechanism of this beneficial treatment is yet to be established. In the present study, an integrated histopathological examination along with molecular biological assay, as well as 1H NMR analysis of multiple biological samples (urine, serum, stomach, cortex and medulla) were employed to systematically assess the pathology of CAG and therapeutic effect of electro-acupuncture stimulation at Sibai (ST 2), Liangmen (ST 21), and Zusanli (ST 36) acupoints located in the stomach meridian using a rat model of CAG. The current results showed that CAG caused comprehensive metabolic alterations including the TCA cycle, glycolysis, membrane metabolism and catabolism, gut microbiota-related metabolism. On the other hand, electro-acupuncture treatment was found able to normalize a number of CAG-induced metabolomics changes by alleviating membrane catabolism, restoring function of neurotransmitter in brain and partially reverse the CAG-induced perturbation in gut microbiota metabolism. These findings provided new insights into the biochemistry of CAG and mechanism of the therapeutic effect of electro-acupuncture stimulations.
Fulltext 1H NMR-based Investigation of Metabolic Response to Electro-Acupuncture Stimulation

Lin C, Wei Z, Cheng KK, Xu J, Shen G, She C, et al.

Sci Rep, 2017 07 28;7(1):6820.
PMID: 28754994 DOI: 10.1038/s41598-017-07306-5

Acupuncture is a traditional Chinese medicine therapy that has been found useful for treating various diseases. The treatments involve the insertion of fine needles at acupoints along specific meridians (meridian specificity). This study aims to investigate the metabolic basis of meridian specificity using proton nuclear magnetic resonance (1H NMR)-based metabolomics. Electro-acupuncture (EA) stimulations were performed at acupoints of either Stomach Meridian of Foot-Yangming (SMFY) or Gallbladder Meridian of Foot-Shaoyang (GMFS) in healthy male Sprague Dawley (SD) rats. 1H-NMR spectra datasets of serum, urine, cortex, and stomach tissue extracts from the rats were analysed by multivariate statistical analysis to investigate metabolic perturbations due to EA treatments at different meridians. EA treatment on either the SMFY or GMFS acupoints induced significant variations in 31 metabolites, e.g., amino acids, organic acids, choline esters and glucose. Moreover, a few meridian-specific metabolic changes were found for EA stimulations on the SMFY or GMFS acupoints. Our study demonstrated significant metabolic differences in response to EA stimulations on acupoints of SMFY and GMFS meridians. These results validate the hypothesis that meridian specificity in acupuncture is detectable in the metabolome and demonstrate the feasibility and effectiveness of a metabolomics approach in understanding the mechanism of acupuncture.
Trial of Spesolimab for Generalized Pustular Psoriasis

Bachelez H, Choon SE, Marrakchi S, Burden AD, Tsai TF, Morita A, et al.

N Engl J Med, 2021 12 23;385(26):2431-2440.
PMID: 34936739 DOI: 10.1056/NEJMoa2111563

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, life-threatening, inflammatory skin disease characterized by widespread eruption of sterile pustules. Interleukin-36 signaling is involved in the pathogenesis of this disorder. Spesolimab, a humanized anti-interleukin-36 receptor monoclonal antibody, is being studied for the treatment of GPP flares.
METHODS: In a phase 2 trial, we randomly assigned patients with a GPP flare in a 2:1 ratio to receive a single 900-mg intravenous dose of spesolimab or placebo. Patients in both groups could receive an open-label dose of spesolimab on day 8, an open-label dose of spesolimab as a rescue medication after day 8, or both and were followed to week 12. The primary end point was a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (range, 0 [no visible pustules] to 4 [severe pustulation]) at the end of week 1. The key secondary end point was a GPPGA total score of 0 or 1 (clear or almost clear skin) at the end of week 1; scores range from 0 to 4, with higher scores indicating greater disease severity.
RESULTS: A total of 53 patients were enrolled: 35 were assigned to receive spesolimab and 18 to receive placebo. At baseline, 46% of the patients in the spesolimab group and 39% of those in the placebo group had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4. At the end of week 1, a total of 19 of 35 patients (54%) in the spesolimab group had a pustulation subscore of 0, as compared with 1 of 18 patients (6%) in the placebo group (difference, 49 percentage points; 95% confidence interval [CI], 21 to 67; P<0.001). A total of 15 of 35 patients (43%) had a GPPGA total score of 0 or 1, as compared with 2 of 18 patients (11%) in the placebo group (difference, 32 percentage points; 95% CI, 2 to 53; P = 0.02). Drug reactions were reported in 2 patients who received spesolimab, in 1 of them concurrently with a drug-induced hepatic injury. Among patients assigned to the spesolimab group, infections occurred in 6 of 35 (17%) through the first week; among patients who received spesolimab at any time in the trial, infections had occurred in 24 of 51 (47%) at week 12. Antidrug antibodies were detected in 23 of 50 patients (46%) who received at least one dose of spesolimab.
CONCLUSIONS: In a phase 2 randomized trial involving patients with GPP, the interleukin-36 receptor inhibitor spesolimab resulted in a higher incidence of lesion clearance at 1 week than placebo but was associated with infections and systemic drug reactions. Longer and larger trials are warranted to determine the effect and risks of spesolimab in patients with pustular psoriasis. (Funded by Boehringer Ingelheim; Effisayil 1 ClinicalTrials.gov number, NCT03782792.).
Fulltext Air quality changes during the COVID-19 lockdown over the Yangtze River Delta Region: An insight into the impact of human activity pattern changes on air pollution variation

Li L, Li Q, Huang L, Wang Q, Zhu A, Xu J, et al.

Sci Total Environ, 2020 Aug 25;732:139282.
PMID: 32413621 DOI: 10.1016/j.scitotenv.2020.139282

The outbreak of COVID-19 has spreaded rapidly across the world. To control the rapid dispersion of the virus, China has imposed national lockdown policies to practise social distancing. This has led to reduced human activities and hence primary air pollutant emissions, which caused improvement of air quality as a side-product. To investigate the air quality changes during the COVID-19 lockdown over the YRD Region, we apply the WRF-CAMx modelling system together with monitoring data to investigate the impact of human activity pattern changes on air quality. Results show that human activities were lowered significantly during the period: industrial operations, VKT, constructions in operation, etc. were significantly reduced, leading to lowered SO2, NOx, PM2.5 and VOCs emissions by approximately 16-26%, 29-47%, 27-46% and 37-57% during the Level I and Level II response periods respectively. These emission reduction has played a significant role in the improvement of air quality. Concentrations of PM2.5, NO2 and SO2 decreased by 31.8%, 45.1% and 20.4% during the Level I period; and 33.2%, 27.2% and 7.6% during the Level II period compared with 2019. However, ozone did not show any reduction and increased greatly. Our results also show that even during the lockdown, with primary emissions reduction of 15%-61%, the daily average PM2.5 concentrations range between 15 and 79 μg m-3, which shows that background and residual pollutions are still high. Source apportionment results indicate that the residual pollution of PM2.5 comes from industry (32.2-61.1%), mobile (3.9-8.1%), dust (2.6-7.7%), residential sources (2.1-28.5%) in YRD and 14.0-28.6% contribution from long-range transport coming from northern China. This indicates that in spite of the extreme reductions in primary emissions, it cannot fully tackle the current air pollution. Re-organisation of the energy and industrial strategy together with trans-regional joint-control for a full long-term air pollution plan need to be further taken into account.
Fulltext Evaluating Approaches for Constructing Polygenic Risk Scores for Prostate Cancer in Men of African and European Ancestry

Darst BF, Shen J, Madduri RK, Rodriguez AA, Xiao Y, Sheng X, et al.

medRxiv, 2023 May 15.
PMID: 37292833 DOI: 10.1101/2023.05.12.23289860

Genome-wide polygenic risk scores (GW-PRS) have been reported to have better predictive ability than PRS based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer risk variants from multi-ancestry GWAS and fine-mapping studies (PRS 269 ). GW-PRS models were trained using a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls used to develop the multi-ancestry PRS 269 . Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California/Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI=0.635-0.677) in African and 0.844 (95% CI=0.840-0.848) in European ancestry men and corresponding prostate cancer OR of 1.83 (95% CI=1.67-2.00) and 2.19 (95% CI=2.14-2.25), respectively, for each SD unit increase in the GW-PRS. However, compared to the GW-PRS, in African and European ancestry men, the PRS 269 had larger or similar AUCs (AUC=0.679, 95% CI=0.659-0.700 and AUC=0.845, 95% CI=0.841-0.849, respectively) and comparable prostate cancer OR (OR=2.05, 95% CI=1.87-2.26 and OR=2.21, 95% CI=2.16-2.26, respectively). Findings were similar in the validation data. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the multi-ancestry PRS 269 constructed with fine-mapping.