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iMSEA: A Novel Metabolite Set Enrichment Analysis Strategy to Decipher Drug Interactions

Wang Y, Liu X, Dong L, Cheng KK, Lin C, Wang X, et al.

Anal Chem, 2023 Apr 18;95(15):6203-6211.
PMID: 37023366 DOI: 10.1021/acs.analchem.2c04603

Drug combinations are commonly used to treat various diseases to achieve synergistic therapeutic effects or to alleviate drug resistance. Nevertheless, some drug combinations might lead to adverse effects, and thus, it is crucial to explore the mechanisms of drug interactions before clinical treatment. Generally, drug interactions have been studied using nonclinical pharmacokinetics, toxicology, and pharmacology. Here, we propose a complementary strategy based on metabolomics, which we call interaction metabolite set enrichment analysis, or iMSEA, to decipher drug interactions. First, a digraph-based heterogeneous network model was constructed to model the biological metabolic network based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Second, treatment-specific influences on all detected metabolites were calculated and propagated across the whole network model. Third, pathway activity was defined and enriched to quantify the influence of each treatment on the predefined functional metabolite sets, i.e., metabolic pathways. Finally, drug interactions were identified by comparing the pathway activity enriched by the drug combination treatments and the single drug treatments. A data set consisting of hepatocellular carcinoma (HCC) cells that were treated with oxaliplatin (OXA) and/or vitamin C (VC) was used to illustrate the effectiveness of the iMSEA strategy for evaluation of drug interactions. Performance evaluation using synthetic noise data was also performed to evaluate sensitivities and parameter settings for the iMSEA strategy. The iMSEA strategy highlighted synergistic effects of combined OXA and VC treatments including the alterations in the glycerophospholipid metabolism pathway and glycine, serine, and threonine metabolism pathway. This work provides an alternative method to reveal the mechanisms of drug combinations from the viewpoint of metabolomics.
Wet wastes to bioenergy and biochar: A critical review with future perspectives

Li J, Li L, Suvarna M, Pan L, Tabatabaei M, Ok YS, et al.

Sci Total Environ, 2022 Jan 07;817:152921.
PMID: 35007594 DOI: 10.1016/j.scitotenv.2022.152921

The ever-increasing rise in the global population coupled with rapid urbanization demands considerable consumption of fossil fuel, food, and water. This in turn leads to energy depletion, greenhouse gas emissions and wet wastes generation (including food waste, animal manure, and sewage sludge). Conversion of the wet wastes to bioenergy and biochar is a promising approach to mitigate wastes, emissions and energy depletion, and simultaneously promotes sustainability and circular economy. In this study, various conversion technologies for transformation of wet wastes to bioenergy and biochar, including anaerobic digestion, gasification, incineration, hydrothermal carbonization, hydrothermal liquefaction, slow and fast pyrolysis, are comprehensively reviewed. The technological challenges impeding the widespread adoption of these wet waste conversion technologies are critically examined. Eventually, the study presents insightful recommendations for the technological advancements and wider acceptance of these processes by establishing a hierarchy of factors dictating their performance. These include: i) life-cycle assessment of these conversion technologies with the consideration of reactor design and catalyst utilization from lab to plant level; ii) process intensification by integrating one or more of the wet waste conversion technologies for improved performance and sustainability; and iii) emerging machine learning modeling is a promising strategy to aid the product characterization and optimization of system design for the specific to the bioenergy or biochar application.
Fulltext Visualization of Combustion Phases of Biomass Particles: Effects of Fuel Properties

Jia Y, Li Z, Wang Y, Wang X, Lou C, Xiao B, et al.

ACS Omega, 2021 Oct 26;6(42):27702-27710.
PMID: 34722970 DOI: 10.1021/acsomega.1c02783

This work established a high-speed camera-assisted visualization system that investigated the effect of volatile matter and fixed carbon content in biomass particles on single-particle combustion phases and their luminous properties. Three types of biomass particles, namely, sawdust (a mixture of pine and willow), corncob, and rice husk, were examined on a Hencken flat-flame burner. The luminous region and intensity of single biomass particles were closely related to the flammability and calorific value of biomass fuel and derived by analyzing a sequence of images captured using a high-speed camera. The combustion temperature was determined through analysis of its radiant energy. The results showed that the ignition mechanisms of volatile matter and fixed carbon corresponded to homogeneous and heterogeneous reactions, respectively. The maximum luminous region values of 1.75 × 106, 2.1 × 106, and 1.0 × 106 μm2 for sawdust (SD), corncob (CC), and rice husk (RH) correlated to the volatile matter content of each biomass sample, which was 69.38, 74.15, and 64.56%, respectively. Because of the high fixed carbon content, the peak temperature of the SD particles could reach 1549 °C. The luminous region and intensity of the combusting particles were significantly affected by the volatile matter and fixed carbon, respectively.
Virtual patient with temporal evolution for mechanical ventilation trial studies: A stochastic model approach

Ang CYS, Chiew YS, Wang X, Ooi EH, Nor MBM, Cove ME, et al.

Comput Methods Programs Biomed, 2023 Oct;240:107728.
PMID: 37531693 DOI: 10.1016/j.cmpb.2023.107728

BACKGROUND AND OBJECTIVE: Healthcare datasets are plagued by issues of data scarcity and class imbalance. Clinically validated virtual patient (VP) models can provide accurate in-silico representations of real patients and thus a means for synthetic data generation in hospital critical care settings. This research presents a realistic, time-varying mechanically ventilated respiratory failure VP profile synthesised using a stochastic model.
METHODS: A stochastic model was developed using respiratory elastance (Ers) data from two clinical cohorts and averaged over 30-minute time intervals. The stochastic model was used to generate future Ers data based on current Ers values with added normally distributed random noise. Self-validation of the VPs was performed via Monte Carlo simulation and retrospective Ers profile fitting. A stochastic VP cohort of temporal Ers evolution was synthesised and then compared to an independent retrospective patient cohort data in a virtual trial across several measured patient responses, where similarity of profiles validates the realism of stochastic model generated VP profiles.
RESULTS: A total of 120,000 3-hour VPs for pressure control (PC) and volume control (VC) ventilation modes are generated using stochastic simulation. Optimisation of the stochastic simulation process yields an ideal noise percentage of 5-10% and simulation iteration of 200,000 iterations, allowing the simulation of a realistic and diverse set of Ers profiles. Results of self-validation show the retrospective Ers profiles were able to be recreated accurately with a mean squared error of only 0.099 [0.009-0.790]% for the PC cohort and 0.051 [0.030-0.126]% for the VC cohort. A virtual trial demonstrates the ability of the stochastic VP cohort to capture Ers trends within and beyond the retrospective patient cohort providing cohort-level validation.
CONCLUSION: VPs capable of temporal evolution demonstrate feasibility for use in designing, developing, and optimising bedside MV guidance protocols through in-silico simulation and validation. Overall, the temporal VPs developed using stochastic simulation alleviate the need for lengthy, resource intensive, high cost clinical trials, while facilitating statistically robust virtual trials, ultimately leading to improved patient care and outcomes in mechanical ventilation.
Viral Characteristics of the Warm Atlantic and Cold Arctic Water Masses in the Nordic Seas

Gao C, Xia J, Zhou X, Liang Y, Jiang Y, Wang M, et al.

Appl Environ Microbiol, 2021 10 28;87(22):e0116021.
PMID: 34469192 DOI: 10.1128/AEM.01160-21

Nordic Seas are the subarctic seas connecting the Arctic Ocean and North Atlantic Ocean with complex water masses, experiencing an abrupt climate change. Though knowledge of the marine virosphere has expanded rapidly, the diversity of viruses and their relationships with host cells and water masses in the Nordic Seas remain to be fully revealed. Here, we establish the Nordic Sea DNA virome (NSV) data set of 55,315 viral contigs including 1,478 unique viral populations from seven stations influenced by both the warm Atlantic and cold Arctic water masses. Caudovirales dominated in the seven NSVs, especially in the warm Atlantic waters. The major giant nucleocytoplasmic large DNA viruses (NCLDVs) contributed a significant proportion of the classified viral contigs in the NSVs (32.2%), especially in the cold Arctic waters (44.9%). The distribution patterns of Caudovirales and NCLDVs were a reflection of the community structure of their hosts in the corresponding water masses and currents. Latitude, pH, and flow speed were found to be key factors influencing the microbial communities and coinfluencing the variation of viral communities. Network analysis illustrated the tight coupling between the variation of viral communities and microbial communities in the Nordic Seas. This study suggests a probable linkage between viromes, host cells, and surface water masses from both the cool Arctic and warm Atlantic Oceans. IMPORTANCE This is a systematic study of Nordic Sea viromes using metagenomic analysis. The viral diversity, community structure, and their relationships with host cells and the complex water masses from both the cool Arctic and the warm Atlantic oceans were illustrated. The NCLDVs and Caudovirales are proposed as the viral characteristics of the cold Arctic and warm Atlantic waters, respectively. This study provides an important background for the viromes in the subarctic seas connecting the Arctic Ocean and North Atlantic Ocean and sheds light on their responses to abrupt climate change in the future.
Variations in knowledge, awareness and treatment of hypertension and stroke risk by country income level

O' Donnell M, Hankey GJ, Rangarajan S, Chin SL, Rao-Melacini P, Ferguson J, et al.

Heart, 2020 Dec 14.
PMID: 33318082 DOI: 10.1136/heartjnl-2019-316515

OBJECTIVE: Hypertension is the most important modifiable risk factor for stroke globally. We hypothesised that country-income level variations in knowledge, detection and treatment of hypertension may contribute to variations in the association of blood pressure with stroke.
METHODS: We undertook a standardised case-control study in 32 countries (INTERSTROKE). Cases were patients with acute first stroke (n=13 462) who were matched by age, sex and site to controls (n=13 483). We evaluated the associations of knowledge, awareness and treatment of hypertension with risk of stroke and its subtypes and whether this varied by gross national income (GNI) of country. We estimated OR and population attributable risk (PAR) associated with treated and untreated hypertension.
RESULTS: Hypertension was associated with a graded increase in OR by reducing GNI, ranging from OR 1.92 (99% CI 1.48 to 2.49) to OR 3.27 (2.72 to 3.93) for highest to lowest country-level GNI (p-heterogeneity<0.0001). Untreated hypertension was associated with a higher OR for stroke (OR 5.25; 4.53 to 6.10) than treated hypertension (OR 2.60; 2.32 to 2.91) and younger age of first stroke (61.4 vs 65.4 years; p<0.01). Untreated hypertension was associated with a greater risk of intracerebral haemorrhage (OR 6.95; 5.61 to 8.60) than ischaemic stroke (OR 4.76; 3.99 to 5.68). The PAR associated with untreated hypertension was higher in lower-income regions, PAR 36.3%, 26.3%, 19.8% to 10.4% by increasing GNI of countries. Lifetime non-measurement of blood pressure was associated with stroke (OR 1.80; 1.32 to 2.46).
CONCLUSIONS: Deficits in knowledge, detection and treatment of hypertension contribute to higher risk of stroke, younger age of onset and larger proportion of intracerebral haemorrhage in lower-income countries.
Fulltext Urinary Sodium and Potassium, and Risk of Ischemic and Hemorrhagic Stroke (INTERSTROKE): A Case-Control Study

Judge C, O'Donnell MJ, Hankey GJ, Rangarajan S, Chin SL, Rao-Melacini P, et al.

Am J Hypertens, 2021 04 20;34(4):414-425.
PMID: 33197265 DOI: 10.1093/ajh/hpaa176

BACKGROUND: Although low sodium intake (<2 g/day) and high potassium intake (>3.5 g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke.
METHODS: We obtained random urine samples from 9,275 cases of acute first stroke and 9,726 matched controls from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes.
RESULTS: Compared with an estimated urinary sodium excretion of 2.8-3.5 g/day (reference), higher (>4.26 g/day) (odds ratio [OR] 1.81; 95% confidence interval [CI], 1.65-2.00) and lower (<2.8 g/day) sodium excretion (OR 1.39; 95% CI, 1.26-1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion >4.26 g/day) was significantly greater (P < 0.001) for intracerebral hemorrhage (ICH) (OR 2.38; 95% CI, 1.93-2.92) than for ischemic stroke (OR 1.67; 95% CI, 1.50-1.87). Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P = 0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (>1.58 g/day) and moderate sodium intake (2.8-3.5 g/day) was associated with the lowest risk of stroke.
CONCLUSIONS: The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for ICH than ischemic stroke. Our data suggest that moderate sodium intake-rather than low sodium intake-combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target.
Fulltext Underwater Turbulence Detection Using Gated Wavefront Sensing Technique

Bi Y, Xu X, Chua SY, Chow EMT, Wang X

Sensors (Basel), 2018 Mar 07;18(3).
PMID: 29518889 DOI: 10.3390/s18030798

Laser sensing has been applied in various underwater applications, ranging from underwater detection to laser underwater communications. However, there are several great challenges when profiling underwater turbulence effects. Underwater detection is greatly affected by the turbulence effect, where the acquired image suffers excessive noise, blurring, and deformation. In this paper, we propose a novel underwater turbulence detection method based on a gated wavefront sensing technique. First, we elaborate on the operating principle of gated wavefront sensing and wavefront reconstruction. We then setup an experimental system in order to validate the feasibility of our proposed method. The effect of underwater turbulence on detection is examined at different distances, and under different turbulence levels. The experimental results obtained from our gated wavefront sensing system indicate that underwater turbulence can be detected and analyzed. The proposed gated wavefront sensing system has the advantage of a simple structure and high detection efficiency for underwater environments.
Fulltext Underwater Object Detection and Reconstruction Based on Active Single-Pixel Imaging and Super-Resolution Convolutional Neural Network

Li M, Mathai A, Lau SLH, Yam JW, Xu X, Wang X

Sensors (Basel), 2021 Jan 05;21(1).
PMID: 33466530 DOI: 10.3390/s21010313

Due to medium scattering, absorption, and complex light interactions, capturing objects from the underwater environment has always been a difficult task. Single-pixel imaging (SPI) is an efficient imaging approach that can obtain spatial object information under low-light conditions. In this paper, we propose a single-pixel object inspection system for the underwater environment based on compressive sensing super-resolution convolutional neural network (CS-SRCNN). With the CS-SRCNN algorithm, image reconstruction can be achieved with 30% of the total pixels in the image. We also investigate the impact of compression ratios on underwater object SPI reconstruction performance. In addition, we analyzed the effect of peak signal to noise ratio (PSNR) and structural similarity index (SSIM) to determine the image quality of the reconstructed image. Our work is compared to the SPI system and SRCNN method to demonstrate its efficiency in capturing object results from an underwater environment. The PSNR and SSIM of the proposed method have increased to 35.44% and 73.07%, respectively. This work provides new insight into SPI applications and creates a better alternative for underwater optical object imaging to achieve good quality.
Tris(8-quinolinolato-N,O)cobalt(III) ethanol solvate

Shanmuga Sundara Raj S, Razak IA, Fun HK, Zhao PS, Jian F, Yang X, et al.

Acta Crystallogr C, 2000 Apr 15;56(Pt 4):E130-1.
PMID: 15263175

In the crystal of the title complex, [Co(C(9)H(6)NO)(3)].C(2)H(5)OH, the central Co atom has a distorted octahedral coordination comprised of three N atoms and three O atoms from the three 8-quinolinolato ligands. The three Co-O bond distances are in the range 1.887 (2)-1.910 (2) A, while the three Co-N bond distances range from 1.919 (2) to 1.934 (2) A. The solvent ethanol molecule forms an intermolecular O-H.O hydrogen bonding with a quinolinolato ligand.
Translation and validation of the Chinese version of the general medication adherence scale (GMAS) in patients with chronic illness

Wang Y, Wang X, Wang X, Naqvi AA, Zhang Q, Zang X

Curr Med Res Opin, 2021 05;37(5):829-837.
PMID: 33719815 DOI: 10.1080/03007995.2021.1901680

OBJECTIVE: To translate the English version of general medication adherence scale (GMAS) into a Chinese version and test its reliability and validity in Chinese patients with chronic diseases.
METHODS: After translating the original English version into Chinese (GMAS-C) following the forward-backward translation and expert review procedure, we conducted a pilot study among 10 chronic disease patients. Each patient took about 10 min to complete the scale and was asked about the difficulty of understanding or filling the scale. Then a total of 312 patients aged 18 years or older with chronic illness were selected from the outpatient departments of two tertiary hospitals and a community center in Tianjin from April 2019 to May 2020 by convenience sampling. Cronbach's α coefficient, item-total correlation and test-retest reliability were used to evaluate the scale reliability; expert evaluation method was used to evaluate the content validity of the scale; and exploratory factor analysis, confirmatory factor analysis, and known group validity were used to evaluate the construct validity of the scale.
RESULTS: As a result of the adaptation process, the GMAS-C's structure was determined. It included 3 dimensions and 11 items and was reliable and valid for Chinese patients with chronic diseases. Total Cronbach's α coefficient of the scale was 0.781 and test-retest reliability coefficient was 0.883 after two weeks. The item-level content validity indexes (CVIs) were ≥ 0.78 for all items. A Kaiser-Meyer-Olkin test and Bartlett' test of sphericity test indicated that the sample met the requirements of factor analysis. Exploratory factor analysis extracted three factors with eigenvalue >1, and 60% of the total variance was explained by three-factor solution. Confirmatory factor analysis showed acceptable fit indices (χ2/df = 1.58, IFI = 0.96, TLI = 0.94, CFI = 0.96 and RMSEA = 0.05).
CONCLUSIONS: The GMAS-C demonstrates satisfactory reliability and validity. This scale can be a clinically useful tool to identify the levels of medication adherence and possible barriers for adherence of the medication regime in patients with chronic diseases.
Fulltext Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case-control study

Wang X, Liu X, O'Donnell MJ, McQueen M, Sniderman A, Pare G, et al.

EClinicalMedicine, 2024 Apr;70:102515.
PMID: 38516107 DOI: 10.1016/j.eclinm.2024.102515

BACKGROUND: Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels.
METHODS: The INTERSTROKE study is a case-control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined).
FINDINGS: Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46-1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61-2.11) than ICH (OR 1.19 95% CI 1.00-1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24-4.10) and PAR (18.6%, 15.1-22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63-2.87) and undetermined cause (OR 1.97, 95% CI 1.55-2.50). Both filtered (OR 1.73, 95% CI 1.50-1.99) and non-filtered (OR 2.59, 95% CI 1.79-3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69-2.27), ischemic stroke (OR 1.89, 95% CI 1.59-2.24) and ICH (OR 2.00, 95% CI 1.60-2.50).
INTERPRETATION: There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke.
FUNDING: The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.
Thyroglobulin determination on silane-antibody functionalized interdigitated dielectrode surface to diagnose thyroid tumor

Wang Y, Sun X, Gopinath SCB, Saheed MSM, Wang X

Biotechnol Appl Biochem, 2022 Feb;69(1):376-382.
PMID: 33538049 DOI: 10.1002/bab.2116

Thyroid cancer appears in endocrine glands and specific to thyroid glands has been reported widely. This work was targeted to identify and quantify thyroglobulin by using antithyroglobulin antibody complexed silane surface on interdigitated electrode (IDE) sensing surface. (3-Aminopropyl)triethoxysilane linker was used to make silane-coupling with antibody and attached on the hydroxylated IDE. This electroanalytical IDE revealed the dose-dependent responses with thyroglobulin concentrations. By getting increments with the thyroglobulin concentrations, the current responses were enhanced concomitantly and the thyroglobulin detection limit was noted as 1 pM on the linear curve [y = 0.1311x + 0.5386; R² = 0.9707] with the sensitivity at lower picomolar range. Moreover, the control experiments with thyroid peroxidase and nonimmune antibody cannot yield any response of current, confirming the specific detection of thyroglobulin. This research set-up is useful to determine and quantify the thyroglobulin and diagnose thyroid cancer.
Fulltext The transcriptional characteristics of NADC34-like PRRSV in porcine alveolar macrophages

Wang P, Ma X, Zhang R, Zhao Y, Hu R, Luo C, et al.

Front Microbiol, 2022;13:1022481.
PMID: 36338035 DOI: 10.3389/fmicb.2022.1022481

The widespread and endemic circulation of porcine reproductive and respiratory syndrome virus (PRRSV) cause persistent financial losses to the swine industry worldwide. In 2017, NADC34-like PRRSV-2 emerged in northeastern China and spread rapidly. The dynamics analysis of immune perturbations associated with novel PRRSV lineage is still incomplete. This study performed a time-course transcriptome sequencing of NADC34-like PRRSV strain YC-2020-infected porcine alveolar macrophages (PAMs) and compared them with JXA1-infected PAMs. The results illustrated dramatic changes in the host's differentially expressed genes (DEGs) presented at different timepoints after PRRSV infection, and the expression profile of YC-2020 group is distinct from that of JXA1 group. Functional enrichment analysis showed that the expression of many inflammatory cytokines was up-regulated following YC-2020 infection but at a significantly lower magnitude than JXA1 group, in line with the trends for most interferon-stimulated genes (ISGs) and their regulators. Meanwhile, numerous components of histocompatibility complex (MHC) class II and phagosome presented a stronger transcription suppression after the YC-2020 infection. All results imply that YC-2020 may induce milder inflammatory responses, weaker antiviral processes, and more severe disturbance of antigen processing and presentation compared with HP-PRRSV. Additionally, LAPTM4A, GLMP, and LITAF, which were selected from weighted gene co-expression network analysis (WGCNA), could significantly inhibit PRRSV proliferation. This study provides fundamental data for understanding the biological characteristics of NADC34-like PRRSV and new insights into PRRSV evolution and prevention.
The prevalence and clinical correlates of suicide attempts in patients with bipolar disorder misdiagnosed with major depressive disorder: Results from a national survey in China

Chen L, Xu YY, Lin JY, Ji ZP, Yang F, Tan S, et al.

Asian J Psychiatr, 2024 Mar;93:103958.
PMID: 38364597 DOI: 10.1016/j.ajp.2024.103958

BACKGROUND AND AIM: Suicide is nearly always associated with underlying mental disorders. Risk factors for suicide attempts (SAs) in patients with bipolar disorder (BD) misdiagnosed with major depressive disorder (MDD) remain unelucidated. This study was to evaluate the prevalence and clinical risk factors of SAs in Chinese patients with BD misdiagnosed with MDD.
METHODS: A total of 1487 patients with MDD from 13 mental health institutions in China were enrolled. Mini International Neuropsychiatric Interview (MINI) was used to identify patients with BD who are misdiagnosed as MDD. The general sociodemographic and clinical data of the patients were collected and MINI suicide module was used to identify patients with SAs in these misdiagnosed patients.
RESULTS: In China, 20.6% of patients with BD were incorrectly diagnosed as having MDD. Among these misdiagnosed patients, 26.5% had attempted suicide. These patients tended to be older, had a higher number of hospitalizations, and were more likely to experience frequent and seasonal depressive episodes with atypical features, psychotic symptoms, and suicidal thoughts. Frequent depressive episodes and suicidal thoughts during depression were identified as independent risk factors for SAs. Additionally, significant sociodemographic and clinical differences were found between individuals misdiagnosed with MDD in BD and patients with MDD who have attempted suicide.
CONCLUSIONS: This study highlights the importance of accurate diagnosis in individuals with BD and provide valuable insights for the targeted identification and intervention of individuals with BD misdiagnosed as having MDD and those with genuine MDD, particularly in relation to suicidal behavior.
The possible hormetic effects of fluorene-9-bisphenol on regulating hypothalamic-pituitary-thyroid axis in zebrafish

Jin M, Dang J, Paudel YN, Wang X, Wang B, Wang L, et al.

Sci Total Environ, 2021 Jul 01;776:145963.
PMID: 33639463 DOI: 10.1016/j.scitotenv.2021.145963

Fluorene-9-bisphenol (BHPF) is a bisphenol A substitute, which has been introduced for the production of so-called 'bisphenol A (BPA)-free' plastics. However, it has been reported that BHPF can enter living organisms through using commercial plastic bottles and cause adverse effects. To date, the majority of the toxicologic study of BHPF focused on investigating its doses above the toxicological threshold. Here, we studied the effects of BHPF on development, locomotion, neuron differentiation of the central nervous system (CNS), and the expression of genes in the hypothalamic-pituitary-thyroid (HPT) axis in zebrafish exposed to different doses of BHPF ranging from 1/5 of LD1 to LD50 (300, 500, 750, 1500, 3000, and 4500 nM). As a result, the possible hormetic effects of BHPF on regulating the HPT axis were revealed, in which low-dose BHPF positively affected the HPT axis while this regulation was inhibited as the dose increased. Underlying mechanism investigation suggested that BHPF disrupted myelination through affecting HPT axis including related genes expression and TH levels, thus causing neurotoxic characteristics. Collectively, this study provides the full understanding of the environmental impact of BHPF and its toxicity on living organisms, highlighting a substantial and generalized ongoing dose-response relationship with great implications for the usage and risk assessment of BHPF.
The main Optimal Post rTpa-Iv Monitoring in Ischemic Stroke Trial (OPTIMISTmain): protocol for a pragmatic, stepped wedge, cluster randomized controlled trial

Ouyang M, Faigle R, Wang X, Johnson B, Summers D, Khatri P, et al.

Cerebrovasc Dis, 2023 Oct 26.
PMID: 37883934 DOI: 10.1159/000534706

Introduction Careful monitoring of patients who receive intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is resource-intensive, and potentially less relevant in those with mild degrees of neurological impairment who are at low-risk of symptomatic intracerebral hemorrhage (sICH) and other complications. \ Methods OPTIMISTmain is an international, multicenter, prospective, stepped wedge, cluster randomized, blinded outcome assessed trial aims to determine whether a less-intensity monitoring protocol is at least as effective, safe and efficient as standard post-IVT monitoring in patients with mild deficits post-AIS. Clinically-stable adult patients with mild AIS (defined by a NIHSS <10) who do not require intensive care within 2 hours post-IVT are recruited at hospitals in Australia, Chile, China, Malaysia, Mexico, UK, US and Vietnam. An average of 15 patients recruited per period (overall 60 patient participants) at 120 sites for a total of 7200 IVT-treated AIS patients will provide 90% power (one-sided α 0.025). The initiation of eligible hospitals is based on a rolling process whenever ready, stratified by country. Hospitals are randomly allocated using permuted blocks into 3 sequences of implementation, stratified by country and the projected number of patients to be recruited over 12 months. These sequences have four periods that dictate the order in which they are to switch from control (usual care) to intervention (implementation of low intensity monitoring protocol) to different clusters of patients in a stepped manner. Compared to standard monitoring, the low-intensity monitoring protocol includes assessments of neurological and vital signs every 15 minutes for 2 hours, 2 hourly (versus every 30 minutes) for 8 hours, and 4 hourly (versus every 1 hour) until 24 hours, post-IVT. The primary outcome measure is functional recovery, defined by the modified Rankin scale (mRS) at 90 days, a seven-point ordinal scale (0 [no residual symptom] to 6 [death]). Secondary outcomes include death or dependency, length of hospital stay, and health-related quality of life, sICH and serious adverse events. Conclusion OPTIMISTmain will provide Level I evidence for the safety and effectiveness of a low-intensity post-IVT monitoring protocol in patients with mild severity of AIS.
Fulltext The impact of aqueous and N-hexane extracts of three Fabaceae species on seed germination and seedling growth of some broadleaved weed species

Safdar ME, Wang X, Abbas M, Ozaslan C, Asif M, Adnan M, et al.

PLoS One, 2021;16(11):e0258920.
PMID: 34739485 DOI: 10.1371/journal.pone.0258920

Weed infestation is a persistent problem for centuries and continues to be major yield reducing issue in modern agriculture. Chemical weed control through herbicides results in numerous ecological, environmental, and health-related issues. Moreover, numerous herbicides have evolved resistance against available herbicides. Plant extracts are regarded as an alternative to herbicides and a good weed management option. The use of plant extracts is environmentally safe and could solve the problem of herbicide resistance. Therefore, laboratory and wire house experiments were conducted to evaluate the phytotoxic potential of three Fabaceae species, i.e., Cassia occidentalis L. (Coffee senna), Sesbania sesban (L.) Merr. (Common sesban) and Melilotus alba Medik. (White sweetclover) against seed germination and seedling growth of some broadleaved weed species. Firstly, N-hexane and aqueous extracts of these species were assessed for their phytotoxic effect against lettuce (Lactuca sativa L.). The extracts found more potent were further tested against germination and seedling growth of four broadleaved weed species, i.e., Parthenium hysterophorus L. (Santa-Maria), Trianthema portulacastrum L. (Pigweed), Melilotus indica L (Indian sweetclover). and Rumex dentatus L. (Toothed dock) in Petri dish and pot experiments. Aqueous extracts of all species were more toxic than their N-hexane forms for seed germination and seedling growth of lettuce; therefore, aqueous extracts were assessed for their phytotoxic potential against four broadleaved weed species. Aqueous extracts of all species proved phytotoxic against T. portulacastrum, P. hysterophorus, M. indica and R. dentatus and retarder their germination by 57, 90, 100 and 58%, respectively. Nevertheless, foliar spray of C. occidentalis extract was the most effective against T. portulacastrum as it reduced its dry biomass by 72%, while M. alba was effective against P. hysterophorus, R. dentatus and M. indica and reduced their dry biomass by 55, 68 and 81%, respectively. It is concluded that aqueous extracts of M. alba, S. sesban and C. occidentalis could be used to retard seed germination of T. portulacastrum, P. hysterophorus, M. indica and R. dentatus. Similarly, aqueous extracts of C. occidentalis can be used to suppress dry biomass of T. portulacastrum, and those of M. alba against P. hysterophorus, R. dentatus. However, use of these extracts needs their thorough testing under field conditions.
The effect of the digital economy on carbon emissions: an empirical study in China

Wang C, Qi F, Liu P, Ibrahim H, Wang X

Environ Sci Pollut Res Int, 2023 Jun;30(30):75454-75468.
PMID: 37219774 DOI: 10.1007/s11356-023-27742-3

Under the new development model, the digital economy has become a new engine to promote the green development of the economy and achieve the goal of "double carbon." Based on panel data from 30 Chinese provinces and cities from 2011 to 2021, the impact of the digital economy on carbon emissions was empirically studied by constructing a panel model and a mediation model. The results show that firstly, the effect of the digital economy on carbon emissions is a non-linear inverted "U" shaped relationship, and this conclusion still holds after a series of robustness tests; secondly, the results of the benchmark regression show that economic agglomeration is an essential mechanism through which the digital economy affects carbon emissions and that the digital economy can indirectly suppress carbon emissions through economic agglomeration. Finally, the results of the heterogeneity analysis show that the impact of the digital economy on carbon emissions varies according to the level of regional development, and its effect on carbon emissions is mainly in the eastern region, while its impact on the central and western regions is weaker, indicating that the impact effect is primarily in developed regions. Therefore, the government should accelerate the construction of new digital infrastructure and implement the development strategy of the digital economy according to local conditions to promote a more significant carbon emission reduction effect of the digital economy.
The discovery of 1, 3-diamino-7H-pyrrol[3, 2-f]quinazoline compounds as potent antimicrobial antifolates

Li Y, Ouyang Y, Wu H, Wang P, Huang Y, Li X, et al.

Eur J Med Chem, 2022 Jan 15;228:113979.
PMID: 34802838 DOI: 10.1016/j.ejmech.2021.113979

The shortage of new antibiotics makes infections caused by gram-negative (G-) bacteria a significant clinical problem. The key enzymes involved in folate biosynthesis represent important targets for drug discovery, and new antifolates with novel mechanisms are urgently needed. By targeting to dihydrofolate reductase (DHFR), a series of 1,3-diamino-7H-pyrrol[3,2-f]quinazoline (PQZ) compounds were designed, and exhibited potent antibacterial activities in vitro, especially against multi-drug resistant G- strains. Multiple experiments indicated that PQZ compounds contain a different molecular mechanism against the typical DHFR inhibitor, trimethoprim (TMP), and the thymidylate synthase (TS) was identified as another potential but a relatively weak target. A significant synergism between the representative compound, OYYF-175, and sulfamethoxazole (SMZ) was observed with a strong cumulative and significantly bactericidal effect at extremely low concentrations (2 μg/mL for SMZ and 0.03 pg/mL for OYYF-175), which could be resulted from the simultaneous inhibition of dihydropteroate synthase (DHPS), DHFR and TS. PQZ compounds exhibited therapeutic effects in a mouse model of intraperitoneal infections caused by Escherichia coli (E. coli). The co-crystal structure of OYYF-175-DHFR was solved and the detailed interactions were provided. The inhibitors reported represent innovative chemical structures with novel molecular mechanism of action, which will benefit the generation of new, efficacious bactericidal compounds.

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