Publications by authors named "Li Zhu"

2,542 Publications

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Impact of a long-term high-fructose diet on systemic metabolic profiles of mice.

FASEB Bioadv 2022 Aug 16;4(8):560-572. Epub 2022 May 16.

Institute of Clinical Pharmacy and Pharmacology Jining First People's Hospital Jining Medical University Jining China.

Evidence is mounting that chronic high-fructose diets (HFrD) can lead to metabolic abnormalities and cause a variety of diseases. However, the underlying mechanism by which long-term high fructose intake influencing systemic metabolism remains unclarified. This study, therefore, attempted to investigate the impact of a high-fructose diet on metabolic profile. Four-week-old male C57BL/6 mice were fed with 15% fructose solution as their only source of water for 8 weeks. Afterward, gas chromatography-mass spectrometry (GC-MS) was employed to investigate the comprehensive metabolic profile of serum, muscle, liver, heart, white adipose, brain, and kidney tissues, and multivariate analyses including principal component analysis (PCA) and orthogonal partial least squared-discriminant analysis (OPLS-DA) were applied to screen for differential metabolite expression between the HFrD and control groups. Furthermore, the MetaboAnalyst 5.0 (http://www.metaboanalyst.ca) and Kyoto Encyclopedia of Genes and Genomes database (KEGG; http://www.kegg.jp) were employed to portray a detailed metabolic network. This study identified 62 metabolites related to HFrD and 10 disturbed metabolic pathways. The results indicated that high fructose intake mainly influenced amino acid metabolism and biosynthesis (glycine, serine, and threonine metabolism; aspartate, and glutamate metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis, and arginine biosynthesis pathways), glutathione metabolism, sphingolipid metabolism, and glyoxylate and dicarboxylate metabolism in serum, whereas these pathways were suppressed in the brain. Starch and sucrose metabolism in muscle was also disrupted. These results elucidate the effects of long-term high fructose consumption on the metabolic profiles of various tissues and provide new insight for the identification of potential metabolic biomarkers and pathways disrupted by high fructose.
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http://dx.doi.org/10.1096/fba.2021-00152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353457PMC
August 2022

Detection of orthologous exons and isoforms using EGIO.

Bioinformatics 2022 Aug 10. Epub 2022 Aug 10.

State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Motivation: Alternative splicing is an important mechanism to generate transcriptomic and phenotypic diversity. Existing methods have limited power to detect orthologous isoforms.

Results: We develop a new method, EGIO, to detect orthologous exons and orthologous isoforms from two species. EGIO uses unique exonic regions to construct exon groups, in which process dynamic programming strategy is used to do exon alignment. EGIO could cover all the coding exons within orthologous genes. A comparison between EGIO and ExTraMapper shows that EGIO could detect more orthologous isoforms with conserved sequence and exon structures. We apply EGIO to compare human and chimpanzee protein-coding isoforms expressed in the frontal cortex and identify 6912 genes that express human unique isoforms. Unexpectedly, more human unique isoforms are detected than those conserved between humans and chimpanzees.

Availability: Source code and test data of EGIO are available at https://github.com/wu-lab-egio/EGIO.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btac548DOI Listing
August 2022

An Insertion Variant in CRH Confers an Increased Risk of Central Serous Chorioretinopathy.

Invest Ophthalmol Vis Sci 2022 Aug;63(9)

Department of Ophthalmology, Eye Disease and Optometry Institute, Peking University People's Hospital, Beijing, China.

Purpose: To identify a novel corticotropin-releasing hormone (CRH) gene variant relevant in patients with central serous chorioretinopathy (CSC).

Methods: We performed a genetic study of CSC in families and sporadic cases with controls. Using whole-exome sequencing and linkage analysis, we identified a heterozygous insertion variant, Gln52insPro, in the CRH gene that cosegregated in two Chinese families with CSC. This variant was evaluated among an additional 1307 patients with CSC and 1438 ethnicity-matched control individuals from three independent Chinese cohorts.

Results: The CRH variant was strongly associated with CSC in these cohorts of Chinese patients (Pmeta = 1.24 × 10-11; odds ratio, 3.01; 95% confidence interval, 2.15-4.21). The risk variant Gln52insPro decreased CRH gene expression.

Conclusions: Our results implicate the hypothalamic-pituitary-adrenal stress response system in the pathogenesis of CSC and provide a novel rationale for therapeutic intervention.
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http://dx.doi.org/10.1167/iovs.63.9.9DOI Listing
August 2022

Predictive value of the combination between the intracranial arterial culprit plaque characteristics and the Essen Stroke Risk Score for short-term stroke recurrence.

J Stroke Cerebrovasc Dis 2022 Aug 3;31(9):106624. Epub 2022 Aug 3.

Department of Radiology, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China. Electronic address:

Aim: In the current study we aim the identification of the culprit plaque characteristics of intracranial arteries using high-resolution magnetic resonance vessel wall imaging (HR-MR-VWI). Moreover, we target the evaluation of the predictive value of culprit plaque characteristics for short-term stroke recurrence combined with ESRS.

Materials And Methods: We conducted a prospective cohort study on 342 patients diagnosed with symptomatic intracranial atherosclerotic stenosis (sICAS), out of which 243 were men and 99 were women with an average age of 64 ± 12 years. 184 cases of anterior circulation ischemia (ACIS) and 158 cases of posterior circulation ischemia (PCIS) were included in the study. All of them underwent HR-MR-VWI during the period between February 2020 and June 2021 in the Second Affiliated Hospital of Nantong University, Nantong, China. The culprit vessel and culprit plaque characteristics were assessed based on HR-MR-VWI images, and the patients' ESRS were obtained from the electronic medical records of the hospital. Concerning the obtained results from the 6-month follow-up, the patients were divided into the non-recurrence group and the recurrence group, and the differences in the above-mentioned features between the two groups were compared. The univariate Cox regression analysis combined with ESRS was performed to screen out the independent risk factors associated with recurrent stroke with P < 0.1. Receiver operating characteristic curves (ROC curves) were plotted to analyze the predictive performance of the culprit plaque characteristics, ESRS and combined variables for stroke recurrence. We used the area under the curve (AUC) ROC, while the sensitivity and specificity were calculated at the optimal threshold. The Delong test was employed to compare the quality of the AUC of the predictors.

Results: A total of 15.5% (53/342) of patients had a stroke recurrence within six months, with statistically significant differences (P < 0.05) between the two groups regarding the ESRS, medical history of diabetes mellitus, myocardial infarction, data for previous acute ischemic stroke (AIS) or transient ischemic attack(TIA), history of peripheral vascular disease, and serum brain natriuretic peptide level. In the patients with ACIS, the incidence of hyperintensity on the T1-weighted imaging (T1WI) was significantly different between the recurrence and the non-recurrence groups (P < 0.05). In the patients with PCIS, statistically significant differences between the recurrence and the non-recurrence group were detected in the culprit plaque burden, degree of enhancement, and incidence of hyperintensity on T1WI (P < 0.05). The ESRS (hazard ratios [HR], 1.598, 95% confidence interval [CI], 1.193-2.141, P = 0.002) ,degree of enhancement (HR = 1.764, 95% CI 0.985-3.087, P = 0.047) and hyperintensity on T1WI (HR = 2.745, 95% CI 1.373-5.488, P = 0.004) proved to be independent risk factors for stroke recurrence. The ESRS predicted stroke recurrence with AUC = 0.618 (95% CI 0.564-0.670), while the best cut-off value was 2 points. Furthermore, the registered sensitivity and specificity were 60.4% and 58.5%, respectively. Regarding the degree of enhancement in the culprit plaque, the prediction of stroke recurrence was with AUC = 0.628 (95% CI 0.574-0.679) as well as with sensitivities and specificities of 58.5% and 64.4%, respectively. Regarding the hyperintensity on T1WI in culprit plaque, the prediction of stroke recurrence was with AUC = 0.678 (95% CI 0.626-0.727) as well as with sensitivities and specificities of 66.0% and 70.0%, respectively. The ESRS combined with the degree of enhancement predicted stroke recurrence with an AUC = 0.685 (95CI% 0.633-0.734), while the recorded sensitivity and specificity were 56.6% and 73.4%, respectively. The ESRS combined with hyperintensity on the T1WI predicted stroke recurrence with an AUC = 0.745 (95CI% 0.696-0.791). The recorded sensitivity and specificity were 64.2% and 76.8%, respectively. The AUC quality of the ESRS combined with hyperintensity on T1WI was higher than that of other indices (P < 0.05).

Conclusions: The hyperintensity on T1WI of the culprit plaque in intracranial arteries combined with ESRS demonstrated better predictive ability for short-term stroke recurrence. We consider this of high importance for clinical application since it provides an easier way of obtaining data for precise diagnosis.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2022.106624DOI Listing
August 2022

Insights of microbial community evolution under benzisothiazolinone exposure in different soil environments.

Chemosphere 2022 Aug 3;307(Pt 2):135868. Epub 2022 Aug 3.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang, 550025, China. Electronic address:

Benzisothiazolinones (1, 2-benzisothiazoline-3-one; BIT) is widely used to control bacterial and fungal diseases of various crops, and their residues in soil may play an important role in the interaction between soil microorganisms. We studied microbial remediation in five representative soils under different soil conditions (unsterilized, sterilized and flooded) using 16S rRNA gene sequencing to investigate the effect of microorganisms on the degradation of BIT residues in soils to minimize the potentially toxic effects of BIT. High-throughput sequencing data showed that the structure and abundance of bacterial communities in BIT soils changed greatly, which might affect their degradation pathways, while Principal Coordinates Analysis (PCoA) results showed that there was no significant difference in the fungal community in different treatments of the five soils, but the degradation rate of BIT was more influenced by anaerobic microorganisms. Furthermore, Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, and Acidobacteria were the predominant bacterial phyla, accounting for 93.74% of all OTUs, which played an important role in the degradation of BIT. Lysinibacillus had a high relative abundance (21.10%) under flooded treatment conditions in Jilin soil, and its bioremediation may be a reason for the rapid degradation of BIT in flooded treatment. Besides, only soil organic matter (SOM) and pH among the soil properties had significant effects on the microbial community. Based on the further analysis of bacterial phenotype, some microorganisms related to the biodegradation of BIT were found, mainly belonging to Proteobacteria, Bacteroidetes and Firmicutes. This study provides a useful theoretical basis for the biodegradation of BIT using isolated microorganisms.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135868DOI Listing
August 2022

Prognosis of systemic inflammation at an early stage of cirrhosis using the monocyte-to-lymphocyte ratio during malnutrition risk screening: a prospective cohort study.

Postgrad Med 2022 Aug 5. Epub 2022 Aug 5.

Department of Infectious Diseases and Hepatopathy, The First Affiliated Hospital of Xi'an Jiaotong University, China.

Objectives: To determine whether the monocyte-to-lymphocyte ratio (MLR), as a systemic inflammation index, predicts malnutrition risk during the early stages of cirrhosis.

Methods: We conducted a single-center prospective cohort study, enrolling patients from June 2016 to September 2020. The patients underwent malnutrition risk assessments upon admission. The patients were classified into five clinical stages according to portal hypertension. The malnutrition risk was scored using the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) and validated by the Nutritional Risk Screening 2002 (NRS-2002) or Liver Disease Undernutrition Screening Tool (LDUST). Routine clinical laboratory measurements were performed to calculate the MLR, Child-Turcotte-Pugh (CTP) class, and model for end-stage liver disease (MELD) score. The patients were followed up for 2 years.

Results: Among the 154 patients with cirrhosis, 60 had compensated cirrhosis and 94 had decompensated cirrhosis. The optimal cutoff value of the MLR, >0.4, was effective in predicting malnutrition related to death or liver transplantation. Those with a high malnutrition risk defined by the NRS-2002 or RFH-NPT had a higher MLR than those with a low malnutrition risk. For patients with class A CTP cirrhosis or a MELD score of <10, an MLR cutoff of <0.4 significantly distinguished more patients with a low malnutrition risk than those with a high malnutrition risk. Both the RFH-NPT score and MLR increased significantly across the decompensated cirrhosis substages. Interestingly, the MLR exhibited a positive correlation with the RFH-NPT score until varices appeared, but the correlation was the highest at the substage of a history of variceal bleeding (r = 0.714, P = 0.009). Multivariable analysis demonstrated that an MLR of >0.4 was an independent factor for malnutrition risk by screening with the RFH-NPT, and this was confirmed using the LDUST and NRS-2002.

Conclusion: Immune-related inflammatory dysfunction predicts malnutrition risk during the early stages of cirrhosis.
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http://dx.doi.org/10.1080/00325481.2022.2110600DOI Listing
August 2022

Relationship Between Prognostic Nutrition Index and New York Heart Association Classification in Patients with Coronary Heart Disease: A RCSCD-TCM Study.

J Inflamm Res 2022 28;15:4303-4314. Epub 2022 Jul 28.

Department of Graduate Schools, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.

Aim: This study aimed to elucidate the relationship between the prognostic nutrition index (PNI) of patients with coronary heart disease (CHD) and the New York Heart Association (NYHA) classification and the complex relationship between PNI combined body mass index (BMI) and NYHA classification.

Methods: The PNI was applied to 17,413 consecutive patients with CHD. Patients were divided into three groups according to PNI: normal nutrition (PNI ≥ 38), moderate malnutrition (35 < PNI < 38), and severe malnutrition (PNI ≤ 35). A total of 2,052 CHD patients with BMI were selected and stratified by combined subgroups of nutritional status and BMI. Logistic regression analysis was used to evaluate the relationship between the PNI and NYHA classification and to adjust for confounding factors.

Results: The prevalence of malnutrition among the 17,413participants with CHD was 4.2%. Moderate and severe malnutrition were significantly related to NYHA class III and V, and the strongest relationship was observed in NYHA class V (odd ratio [OR]: 6.564; 95% confidence interval [CI]: 4.043-10.658). Malnourished-underweight patients and malnourished-overweight patients were significantly associated with higher NYHA classification, and malnourished-underweight patients (OR: 8.038; 95% CI: 2.091-30.892) were significantly more than malnourished-overweight patients (OR: 3.580; 95% CI: 1.286-9.966).

Conclusion: There were differences in the NYHA classification of CHD patients with different nutritional statuses. The lower the PNI, the worse the NYHA classification of CHD patients. Malnourished-underweight patients had a worse NYHA classification than malnourished-overweight patients.
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http://dx.doi.org/10.2147/JIR.S371045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342891PMC
July 2022

Identification of the Highly Active Co-N Coordination Motif for Selective Oxygen Reduction to Hydrogen Peroxide.

J Am Chem Soc 2022 Aug 3. Epub 2022 Aug 3.

Hunan Joint International Research Center for Carbon Dioxide Resource Utilization, State Key Laboratory of Powder Metallurgy, School of Physical and Electronics, Central South University, 410083 Changsha, China.

Electrosynthesis of hydrogen peroxide (HO) through oxygen reduction reaction (ORR) is an environment-friendly and sustainable route for obtaining a fundamental product in the chemical industry. Co-N single-atom catalysts (SAC) have sparkled attention for being highly active in both 2e ORR, leading to HO and 4e ORR, in which HO is the main product. However, there is still a lack of fundamental insights into the structure-function relationship between CoN and the ORR mechanism over this family of catalysts. Here, by combining theoretical simulation and experiments, we unveil that pyrrole-type CoN (Co-N SAC) is mainly responsible for the 2e ORR, while pyridine-type CoN catalyzes the 4e ORR. Indeed, Co-N SAC exhibits a remarkable HO selectivity of 94% and a superb HO yield of 2032 mg for 90 h in a flow cell, outperforming most reported catalysts in acid media. Theoretical analysis and experimental investigations confirm that Co-N SAC─with weakening O/HOO* interaction─boosts the HO production.
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http://dx.doi.org/10.1021/jacs.2c01194DOI Listing
August 2022

The clinical significance and function of EGFR mutation in TKI treatments of NSCLC patients.

Cancer Biomark 2022 Jul 22. Epub 2022 Jul 22.

Department of Geriatrics, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.

Background: EGFR mutations widely exists in NSCLC patients, which are involved in cancer development.

Objective: The function of EGFR mutations in the resistance to TKI treatments of NSCLC was evaluated to provide theoretical support for the clinical management of NSCLC patients.

Methods: A total of 150 NSCLC patients including 118 patients with EGFR mutation and 32 without, were included in this study. The EGFR mutation status and subtypes were analyzed in recruited patients. The distribution of EGFR mutation subtypes and their association with clinicopathological features were also assessed. The prognostic value of EGFR mutation was evaluated by the overall survival of recruited patients. The function of EGFR mutation was estimated, in vitro, in the TKI resistant NSCLC cells with different subtypes of EGFR mutation.

Results: The exon 19 deletion was the most common subtype of EGFR mutation in the enrolled patients followed by the exon 21 L858R point mutation. The EGFR mutations were closely associated with the differentiation degree and the histological types of NSCLC cases. EGFR mutation was an independent prognostic factor of NSCLC with a close relationship with the overall survival of patients. The exon 20 T790M mutation results in the erlotinib resistance through EGFR/PI3K/Akt signaling pathway.

Conclusions: The EGFR mutation is a critical factor in the prognosis and for the resistance to TKI treatment in NSCLC. The exon 20 T790M mutation was involved in the erlotinib resistance through PI3K/Akt signaling pathway.
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http://dx.doi.org/10.3233/CBM-210281DOI Listing
July 2022

Isolation of Bioactive Compounds, Antibacterial Activity, and Action Mechanism of Spore Powder From xj.

Front Microbiol 2022 11;13:934857. Epub 2022 Jul 11.

Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), College of Life Sciences, Institute of Agro-Bioengineering, Guizhou University, Guiyang, China.

fungi can produce a wide range of secondary metabolites, and they have represented a potential resource of novel bioactive compounds. Bacterial plant diseases have a serious impact on the sustainable development of agriculture worldwide, so it is necessary to use natural antibacterial compounds in microorganisms to control plant pathogens. This study was conducted to investigate the bioactive compounds of xj, three plant pathogens ( T-37, EC-1, and RS-2) were used as indicator bacteria, according to the biological activity tracking, five compounds were isolated from xj spore powder, and characterization of compounds was done by NMR (H-NMR and C-NMR) and EI-MS and was identified as ergosterol (1), β-sitosterol (2), 5-pentadecylresorcinol (3), 5-hydroxymethyl-2-furancarboxylic acid (4), and succinimide (5). Compounds 3 and 5 were isolated from xj for the first time. The minimum inhibitory concentration (MIC) of five compounds against three plant pathogens was evaluated, the results showed that compound 4 exhibited the strongest antibacterial activity against tested bacteria, and RS-2 was the most sensitive to compound 4, showing the lowest MIC of 15.56 μg/ml. We concluded that the mechanism of action of the compound 4 against RS-2 might be described as compound 4 acting on bacterial protein synthesis and intracellular metabolism according to the results of the scanning electron microscopy observation, permeability of cell membrane and SDS-PAGE. These results indicated that compound 4 has good potential to be as a biocontrol agent. In conclusion, the results from this study demonstrated that the compounds with antibacterial activity are of great significance of the prevention and control of plant phytopathogenic bacteria, and they may be applicable to exploring alternative approaches to integrated control of phytopathogens.
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http://dx.doi.org/10.3389/fmicb.2022.934857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309528PMC
July 2022

Emerging mechanisms of pyroptosis and its therapeutic strategy in cancer.

Cell Death Discov 2022 Jul 27;8(1):338. Epub 2022 Jul 27.

Department of Oncology, NHC Key Laboratory of Cancer Proteomics & State Local Joint Engineering Laboratory for Anticancer Drugs, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China.

Pyroptosis, a type of inflammatory programmed cell death, is triggered by caspase cleavage of gasdermin family proteins. Based on accumulating evidence, pyroptosis is closely associated with tumour development, but the molecular mechanism underlying pyroptosis activation and the signalling pathways regulated by pyroptosis remain unclear. In this review, we first briefly introduce the definition, morphological characteristics, and activation pathways of pyroptosis and the effect of pyroptosis on anticancer immunity. Then we review recent progress concerning the complex role of pyroptosis in various tumours. Importantly, we summarise various FDA-approved chemotherapy drugs or natural compounds that exerted antitumor properties by inducing pyroptosis of cancer cells. Moreover, we also focus on the current application of nanotechnology-induced pyroptosis in tumour therapy. In addition, some unsolved problems and potential future research directions are also raised.
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http://dx.doi.org/10.1038/s41420-022-01101-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329358PMC
July 2022

Factors Associated with White Fat Browning: New Regulators of Lipid Metabolism.

Int J Mol Sci 2022 Jul 11;23(14). Epub 2022 Jul 11.

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.

Mammalian adipose tissue can be divided into white and brown adipose tissue based on its colour, location, and cellular structure. Certain conditions, such as sympathetic nerve excitement, can induce the white adipose adipocytes into a new type of adipocytes, known as beige adipocytes. The process, leading to the conversion of white adipocytes into beige adipocytes, is called white fat browning. The dynamic balance between white and beige adipocytes is closely related to the body's metabolic homeostasis. Studying the signal transduction pathways of the white fat browning might provide novel ideas for the treatment of obesity and alleviation of obesity-related glucose and lipid metabolism disorders. This article aimed to provide an overview of recent advances in understanding white fat browning and the role of BAT in lipid metabolism.
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http://dx.doi.org/10.3390/ijms23147641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325132PMC
July 2022

Paper-Based Fluidic Sensing Platforms for β-Adrenergic Agonist Residue Point-of-Care Testing.

Biosensors (Basel) 2022 Jul 12;12(7). Epub 2022 Jul 12.

Department of Biochemistry and Molecular Biology, School of Medicine, Tulane University, New Orleans, LA 70112, USA.

The illegal use of β-adrenergic agonists during livestock growth poses a threat to public health; the long-term intake of this medication can cause serious physiological side effects and even death. Therefore, rapid detection methods for β-adrenergic agonist residues on-site are required. Traditional detection methods such as liquid chromatography have limitations in terms of expensive instruments and complex operations. In contrast, paper methods are low cost, ubiquitous, and portable, which has led to them becoming the preferred detection method in recent years. Various paper-based fluidic devices have been developed to detect β-adrenergic agonist residues, including lateral flow immunoassays (LFAs) and microfluidic paper-based analytical devices (μPADs). In this review, the application of LFAs for the detection of β-agonists is summarized comprehensively, focusing on the latest advances in novel labeling and detection strategies. The use of μPADs as an analytical platform has attracted interest over the past decade due to their unique advantages and application for detecting β-adrenergic agonists, which are introduced here. Vertical flow immunoassays are also discussed for their shorter assay time and stronger multiplexing capabilities compared with LFAs. Furthermore, the development direction and prospects for the commercialization of paper-based devices are considered, shedding light on the development of point-of-care testing devices for β-adrenergic agonist residue detection.
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http://dx.doi.org/10.3390/bios12070518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313176PMC
July 2022

Potential Cross Talk between Autism Risk Genes and Neurovascular Molecules: A Pilot Study on Impact of Blood Brain Barrier Integrity.

Cells 2022 Jul 15;11(14). Epub 2022 Jul 15.

Department of Neurology, Pediatric Research Institute, Louisville, KY 40202, USA.

Autism Spectrum Disorder (ASD) is a common pediatric neurobiological disorder with up to 80% of genetic etiologies. Systems biology approaches may make it possible to test novel therapeutic strategies targeting molecular pathways to alleviate ASD symptoms. A clinical database of autism subjects was queried for individuals with a copy number variation (CNV) on microarray, Vineland, and Parent Concern Questionnaire scores. Pathway analyses of genes from pathogenic CNVs yielded 659 genes whose protein-protein interactions and mRNA expression mapped 121 genes with maximal antenatal expression in 12 brain regions. A Research Domain Criteria (RDoC)-derived neural circuits map revealed significant differences in anxiety, motor, and activities of daily living skills scores between altered CNV genes and normal microarrays subjects, involving Positive Valence (reward), Cognition (IQ), and Social Processes. Vascular signaling was identified as a biological process that may influence these neural circuits. Neuroinflammation, microglial activation, iNOS and 3-nitrotyrosine increase in the brain of Semaphorin 3F- Neuropilin 2 (Sema 3F-NRP2) KO, an ASD mouse model, agree with previous reports in the brain of ASD individuals. Signs of platelet deposition, activation, release of serotonin, and albumin leakage in ASD-relevant brain regions suggest possible blood brain barrier (BBB) deficits. Disruption of neurovascular signaling and BBB with neuroinflammation may mediate causative pathophysiology in some ASD subgroups. Although preliminary, these data demonstrate the potential for developing novel therapeutic strategies based on clinically derived data, genomics, cognitive neuroscience, and basic neuroscience methods.
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http://dx.doi.org/10.3390/cells11142211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315816PMC
July 2022

Monitoring CAR19 T Cell Population by Flow Cytometry and its Consistency with ddPCR.

Cytometry A 2022 Jul 25. Epub 2022 Jul 25.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Anti-CD19 Chimeric antigen receptor (CAR19) T cell therapy has produced impressive clinical efficacy in patients with relapsed or refractory B-cell malignancies. As a living drug, monitoring the pharmacokinetics of CAR T cells in vivo is an important part of clinical work, which provides valuable information for assessing therapeutic response and related side effects. However, no guidelines are available regarding the detection and quantification of CAR T cells. Flow cytometry is a convenient and commonly used method in monitoring CAR T cell kinetics, but its performance remains to be validated.

Methods: By using a commercial anti-idiotype antibody that detects unique epitopes on the most popular CAR19 construct, we evaluated important performance parameters, including specificity, lower limit of detection, lower limit of quantification, and precision of flow cytometry in the detection and quantification of CAR19 T cells. Consistency between the results generated by flow cytometry and droplet digital PCR was then investigated in 188 pairs of clinical data and in cell line experiments.

Results: Rabbit anti-mouse FMC63 monoclonal antibody possesses high specificity in the detection of CAR19 positive cells by FCM with a cut-off value of 0.05%. The results produced by flow cytometry and ddPCR were well correlated in the clinical samples and in cell lines, but the correlation deteriorated as the abundance of CAR19 positive cells decreased. This was especially evident with less than 0.5% of lymphocytes in clinical data, possibly due to reduced precision (indicated by intra- and inter-assay coefficients of variability) of both droplet digital PCR and flow cytometry.

Conclusion: We demonstrated that flow cytometry using anti-idiotype antibody is a reliable and robust approach in the detection and quantification of CAR19 T cells in vivo and has good consistency with droplet digital PCR in monitoring CAR19 T cell kinetics. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/cyto.a.24676DOI Listing
July 2022

CT-Based Radiomics Nomogram Improves Risk Stratification and Prediction of Early Recurrence in Hepatocellular Carcinoma After Partial Hepatectomy.

Front Oncol 2022 7;12:896002. Epub 2022 Jul 7.

Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, China.

Objectives: To develop and validate an intuitive computed tomography (CT)-based radiomics nomogram for the prediction and risk stratification of early recurrence (ER) in hepatocellular carcinoma (HCC) patients after partial hepatectomy.

Methods: A total of 132 HCC patients treated with partial hepatectomy were retrospectively enrolled and assigned to training and test sets. Least absolute shrinkage and selection operator and gradient boosting decision tree were used to extract quantitative radiomics features from preoperative contrast-enhanced CT images of the HCC patients. The radiomics features with predictive value for ER were used, either alone or in combination with other predictive features, to construct predictive models. The best performing model was then selected to develop an intuitive, simple-to-use nomogram, and its performance in the prediction and risk stratification of ER was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA).

Results: The radiomics model based on the radiomics score (Rad-score) achieved AUCs of 0.870 and 0.890 in the training and test sets, respectively. Among the six predictive models, the combined model based on the Rad-score, Edmondson grade, and tumor size had the highest AUCs of 0.907 in the training set and 0.948 in the test set and was used to develop an intuitive nomogram. Notably, the calibration curve and DCA for the nomogram showed good calibration and clinical application. Moreover, the risk of ER was significantly different between the high- and low-risk groups stratified by the nomogram (0.001).

Conclusions: The CT-based radiomics nomogram developed in this study exhibits outstanding performance for ER prediction and risk stratification. As such, this intuitive nomogram holds promise as a more effective and user-friendly tool in predicting ER for HCC patients after partial hepatectomy.
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http://dx.doi.org/10.3389/fonc.2022.896002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302642PMC
July 2022

Remnant cholesterol for the detection of glucose metabolic states in patients with coronary heart disease angina pectoris.

Acta Diabetol 2022 Jul 23. Epub 2022 Jul 23.

Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.

Background: This study aimed to evaluate the relationship between remnant cholesterol (RC) and glucose metabolic states in coronary heart disease (CHD) patients with angina pectoris.

Methods: This study collected data from 11,557 CHD patients with angina pectoris aged 35-75 years in Tianjin, China. Participants were divided into normal glucose regulation (NGR), prediabetes (Pre-DM) and diabetes mellitus (DM) groups according to glucose metabolic states. Linear regression analysis was used to explore the relationship between glucose metabolism [fasting blood glucose (FBG) and glycated hemoglobin (HbA1c)] and RC levels. Logistic regression was performed to analyze the relationship between RC levels and glucose metabolic states.

Results: Among all participants, 5883 (50.9%) had a DM state and 4034 (34.9%) had a Pre-DM state. FBG levels and HbA1c levels were positively related with RC in all patients (P < 0.001). NGR was used as a reference, multi-adjusted model showing that RC level was significantly associated with Pre-DM [Odds ratio (OR): 1.37; 95% confidence interval (CI) 1.19-1.56; P < 0.001] and DM state (OR:1.47; 95% CI 1.29-1.67; P < 0.001). When considering RC as categorical variables (tertiles), using T1 as a reference, T3 had the strongest relationship between RC levels and Pre-DM and DM state in univariate model and multivariate model. In the stratified analyses, the association between RC levels and pre-DM and DM in women was higher than that in men, and the elderly patients was higher than in the middle-aged patients.

Conclusion: The study demonstrated a significant association between RC levels and pre-DM and DM state among CHD patients with angina pectoris, and the relationship was stronger in women and elderly patients.
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http://dx.doi.org/10.1007/s00592-022-01935-7DOI Listing
July 2022

Total Barley Maiya Alkaloids Prevent Increased Prolactin Levels Caused by Antipsychotic Drugs and Reduce Dopamine Receptor D2 Epigenetic Mechanisms.

Front Pharmacol 2022 5;13:888522. Epub 2022 Jul 5.

Pharmacy Department of Wuhan University Tongren Hospital (The Third Hospital of Wuhan), Wuhan, China.

The dopamine D2 receptor (DRD2) plays an important role in the increased prolactin (PRL) levels associated with the pathogenesis of antipsychotic drugs (ADs). Elevated prolactin levels can affect people's quality of life. Maiya alkaloids has been used to treat diseases associated with high PRL levels. Maiya, is a processed product of the mature fruits of Hordeum vulgare L. (a gramineous plant) after sprouting and drying and also a common Chinese herbal drug used in the clinic, is traditionally used to treat abnormal lactation, and is currently used clinically for the treatment of abnormal PRL levels. Epigenetic mechanisms can be related to DRD2 expression. We investigated the role of DRD2 methylation in the induction of PRL expression by ADs and the mechanism underlying the effects of total barley maiya alkaloids (TBMA) on this induction. The methylation rate of DRD2 in 46 people with schizophrenia who took risperidone was detected by MassARRAY sequencing. Humans were long term users of Ris. Seventy Sprague Dawley female rats were divided into seven groups. A rat model of risperidone-induced PRL was established, and the potential protective effects of TBMA and its components [e.g., hordenine (Hor)] on these increased PRL levels were investigated. The PRL concentration was detected by Enzyme-linked immunosorbent assay. PRL, DRD2, and DNA methyltransferase (DNMT1, DNMT3α, and DNMT3β) protein and mRNA expression were detected by western blotting and real-time polymerase chain reaction (RT-PCR), respectively. The positive rate of methylation in the DRD2 promoter region of rats was detected by MassARRAY sequencing. Clinical studies showed that the positive rate of DRD2 methylation associated with increased PRL levels induced by ADs was significantly higher than in the normal prolactinemia (NPRL) group. and vitro, TBMA and Hor inhibited this induction of PRL expression and increased DRD2 expression by inhibiting the expression of the DNMTs. TBMA and hordenine increased DRD2 expression by inhibiting DNMT-dependent DRD2 methylation.
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http://dx.doi.org/10.3389/fphar.2022.888522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294270PMC
July 2022

Analysis on the Key Influence of Adolescent Health Information Literacy Using Big Data Analysis Technology under Social Network Environment.

J Environ Public Health 2022 11;2022:4126217. Epub 2022 Jul 11.

School of Visual Arts and Design, Changchun Guanghua University, Changchun 130022, China.

. This paper aims to explore the influence mechanism of adolescent health information literacy on health behavior. . 13-19 year olds are taken as the survey objects to investigate their health information literacy through a questionnaire. Health information literacy mainly includes health information needs, acquisition, evaluation, use, and behaviors. A total of 252 adolescents' data were collected in this study, and model testing was performed with the help of regression analysis and structural equation modeling. . The results of the study show that adolescents' health information needs, acquisition, evaluation, and application abilities have a positive impact on health behaviors in the social network environment. Emotional responses and individual cognition as intermediate variables play important roles between health information literacy and health behaviors. Health information needs and health information assessments have the highest impact on mental health and social health, respectively. The society should pay special attention to the influence of adolescents' health cognition and anxiety on health behavior in the context of social network.
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http://dx.doi.org/10.1155/2022/4126217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293561PMC
July 2022

pH-Responsive hyaluronic acid-enveloped ZIF-8 nanoparticles for anti-atherosclerosis therapy.

Biomater Sci 2022 Jul 20. Epub 2022 Jul 20.

Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Modern Life Science Experiment Teaching Center at Bioengineering College of Chongqing University, Chongqing 400030, China.

Nanomedicines represent new promising strategies for treating atherosclerosis (AS), because they enhance drug bioavailability and have lower side effects. Nevertheless, nanomedicines have several challenges with these advantages, including a limited circulation life, lack of precise targeting, and insufficient control of drug release. Accordingly, the development of drug delivery systems (DDSs) with abilities to enhance the payload delivery to the AS plaque lesion and to control drug release can boost the therapeutic efficacy and safety for AS treatment. Herein, we employed a one-step self-assembly approach for effectively encapsulating the anti-AS drug simvastatin (SIM) in zeolitic imidazolate framework-8 (ZIF-8) (SIM/ZIF-8), and then coated it with hyaluronic acid (HA) to fabricate the SIM/[email protected] nanoplatform. The resulting nanoplatform could efficiently accumulate in plaque regions through the specific recognition between HA and CD44. Meanwhile, the acid environment breaks down ZIF-8 to release SIM. The and experiments demonstrated that SIM/[email protected] could inhibit the proliferation of smooth muscle cells and have good biocompatibility. Moreover, SIM/[email protected] can effectively suppress the development of AS plaques without any considerable side effects in mice treatments. The findings revealed that SIM/[email protected] may be a promising nanomedicine for safe and efficient anti-AS applications.
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http://dx.doi.org/10.1039/d2bm00603kDOI Listing
July 2022

A GC-MS-based untargeted metabolomics approach for comprehensive metabolic profiling of vancomycin-induced toxicity in mice.

Heliyon 2022 Jul 6;8(7):e09869. Epub 2022 Jul 6.

Institute of Clinical Pharmacy and Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272000, China.

Background: Vancomycin is a glycopeptide antibiotic that is commonly used for severe drug-resistant infections treatment. Application of vancomycin frequently leads to severe ototoxicity, hepatotoxicity, and nephrotoxicity; however, the comprehensive metabolic analysis of vancomycin-induced toxicity is lacking.

Purpose: This study attempted to investigate the metabolic changes after vancomycin administration in mice.

Methods: Experimental mice (n = 9) received continuous intraperitoneal injection of vancomycin (400 mg/kg) every day for 7 days, and mice in control group (n = 9) were treated with the same amount of normal saline. Pathological changes of the kidney were examined using haematoxylin and eosin (HE) staining. A gas chromatography-mass spectrometry (GC-MS) approach was used to identify discriminant metabolites in serum and various organs including the heart, liver, kidney, spleen, cerebral cortex, hippocampus, inner ear, lung, and intestine. The potential metabolites were identified using orthogonal partial least squares discrimination analysis (OPLS-DA). Subsequently, the MetaboAnalyst 5.0 (http://www.metaboanalyst.ca) and Kyoto Encyclopedia of Genes and Genomes database (KEGG, http://www.kegg.jp) were employed to depict the metabolic pathways.

Results: Compared with the control group, the vancomycin induced 13, 17, 27, 22, 16, 10, 17, 11, 10, and 7 differential metabolites in the serum, liver, kidney, heart, cerebral cortex, lung, spleen, intestine, hippocampus, and inner ear, respectively. Further pathway analyses identified that amino acids metabolism, fatty acids biosynthesis, energy metabolism, and lipid metabolism were disrupted after VCM exposure.

Conclusion: Vancomycin affects the metabolism in various organs in mice, which provides new insights for identification of vancomycin-induced toxicity, and facilitate to better understanding of the metabolic pathogenesis of vancomycin.
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http://dx.doi.org/10.1016/j.heliyon.2022.e09869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287194PMC
July 2022

Toripalimab combined with concurrent platinum-based Chemoradiotherapy in patients with locally advanced cervical Cancer: an open-label, single-arm, phase II trial.

BMC Cancer 2022 Jul 19;22(1):793. Epub 2022 Jul 19.

Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.

Background: Concurrent chemoradiotherapy is currently the standard of care for patients with locally advanced cervical cancer. However, even with the application of modern radiotherapy techniques, a considerable number of patients still develop distant metastases. PD-L1 inhibitors show good efficacy in cervical cancer. This single-arm phase II study aims to explore the efficacy and tolerability of combining PD-L1 inhibitor with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer.

Methods/design: The primary endpoint of the study was the objective response rate assessed according to RECIST v1.1 criteria. The inclusion criteria were previously untreated patients aged 18-75 years with stage III-IVA (FIGO 2018 staging system) locally advanced cervical cancer. During concurrent chemoradiotherapy and consolidation chemotherapy, the enrolled patients will receive toripalimab (240 mg) every 3 weeks. After consolidation chemotherapy, the enrolled patients will be treated with toripalimab (240 mg) once every 6 weeks until the whole treatment cycle reaches 1 year. Intensity modulated radiotherapy was used for external beam radiation, and high-dose rate brachytherapy was delivered under image-guidance. Weekly DDP (40 mg/m) was given concurrently with radiotherapy while 6 cycles of consolidated chemotherapy (paclitaxel plus DDP) were given after radiotherapy every three weeks. Secondary objectives included safety and tolerability, toxicity profile, progression-free survival, and overall survival.

Discussion: PD-L1 inhibitor has shown good efficacy in recurrent/metastatic cervical cancer. However, there is still a lack of evidence about its combination with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer. The purpose of this study is to explore the efficacy and tolerance of this combination therapy, so as to lay the foundation for the future phase III randomized study.

Trial Registration:  clinicaltrials.gov NCT05084677 . Retrospectively registered on Octorber 07, 2021.
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http://dx.doi.org/10.1186/s12885-022-09866-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295395PMC
July 2022

Clinical metabolomic analysis of Danlou tablets with antioxidant effects for treating stable angina pectoris.

J Pharm Biomed Anal 2022 Jul 1;219:114922. Epub 2022 Jul 1.

Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin 301617, China. Electronic address:

The Danlou tablets (DLT) is a patented Chinese medicine that can effectively ameliorate coronary heart disease- and angina pectoris-related chest congestion and pain. However, the mechanism underlying the therapeutic effects of DLT in the context of stable angina pectoris (SAP) has not been clearly elucidated. In this study, ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to analyze serum samples from patients with SAP before and after DLT administration. The results of metabolomic analyses were verified biologically, and the mechanisms of action of DLT with respect to treating SAP were elucidated. Nineteen biomarkers were identified. Among these biomarkers, the levels of 15 reverted to those corresponding to a healthy state following DLT treatment. The main metabolic pathways associated with the functions of DLT in SAP were energy metabolism, purine metabolism, glycerophospholipid metabolism and amino acid metabolism, all of which are related to oxidative stress. Biological verification revealed that DLT decreased the expression of the oxidative stress indicators, xanthine oxidase (XOD) and malondialdehyde (MDA), and increased heme oxygenase-1 (HO-1) expression and superoxide dismutase (SOD) activity. Taken together, we revealed that DLT effectively ameliorates SAP by adjusting the oxidative stress status. This study provided an objective index for evaluating the efficacy of DLT for treating SAP.
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http://dx.doi.org/10.1016/j.jpba.2022.114922DOI Listing
July 2022

Attention allocation on mobile app interfaces when human interacts with them.

Cogn Neurodyn 2022 Aug 27;16(4):859-870. Epub 2021 Dec 27.

School of Computer Science and Electronic Engineering, University of Essex, Colchester, CO4 3SQ UK.

With the popularity of smartphones and the pervasion of mobile apps, people spend more and more time to interact with a diversity of apps on their smartphones, especially for young population. This raises a question: how people allocate attention to interfaces of apps during using them. To address this question, we, in this study, designed an experiment with two sessions (i.e., Session1: browsing original interfaces; Session 2: browsing interfaces after removal of colors and background) integrating with an eyetracking system. Attention fixation durations were recorded by an eye-tracker while participants browsed app interfaces. The whole screen of smartphone was divided into four even regions to explore fixation durations. The results revealed that participants gave significantly longer total fixation duration on the bottom left region compared to other regions in the session (1) Longer total fixation duration on the bottom was preserved, but there is no significant difference between left side and right side in the session2. Similar to the finding of total fixation duration, first fixation duration is also predominantly paid on the bottom area of the interface. Moreover, the skill in the use of mobile phone was quantified by assessing familiarity and accuracy of phone operation and was investigated in the association with the fixation durations. We found that first fixation duration of the bottom left region is significantly negatively correlated with the smartphone operation level in the session 1, but there is no significant correlation between them in the session (2) According to the results of ratio exploration, the ratio of the first fixation duration to the total fixation duration is not significantly different between areas of interest for both sessions. The findings of this study provide insights into the attention allocation during browsing app interfaces and are of implications on the design of app interfaces and advertisements as layout can be optimized according to the attention allocation to maximally deliver information.
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http://dx.doi.org/10.1007/s11571-021-09760-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279534PMC
August 2022

Correlation of the characteristics of symptomatic intracranial atherosclerotic plaques with stroke types and risk of stroke recurrence: a cohort study.

Ann Transl Med 2022 Jun;10(12):658

Department of Radiology, The Second Affiliated Hospital of Nantong University, Nantong, China.

Background: Symptomatic intracranial atherosclerotic stenosis (sICAS) patients had a higher risk of stroke recurrence, and the risk of acute ischemic stroke (AIS) was higher than transient ischemic attack (TIA). Therefore, it is important to explore the risk factors associated with sICAS clinical subtypes and the risk of stroke recurrence. The purpose of this study was to investigate the association between intracranial arterial culprit plaque characteristics with sICAS clinical subtypes and the risk of stroke recurrence.

Methods: A total of 206 patients with sICAS were included. Baseline demographic data and relevant serologic indices were collected from all participants. All participants were assessed by high-resolution vessel wall imaging (HR-VWI) for culprit vessel and culprit plaque characteristics. The follow-up method was outpatient or telephone follow-up. Associated factors for sICAS clinical subtypes were analyzed by binary logistic regression. Cox proportional hazard regression analysis were used to analysis the independent risk factors for recurrent stroke.

Results: In this group, there were 154 patients with AIS, 52 patients with TIA, 124 patients with anterior circulation ischemic symptom (ACiS), and 82 patients with posterior circulation ischemic symptom (PCiS). Male gender [odds ratio (OR) =5.575, 95% confidence interval (CI): 2.120 to 14.658], history of previous statin use (OR =0.309, 95% CI: 0.113 to 0.843) and serum apolipoprotein A/B values (OR =0.363, 95% CI: 0.139 to 0.948) were associated factors for AIS. A total of 24 patients (11.7%) experienced stroke recurrence during the 1-year follow-up period. Hyperintensity on T1 weighted imaging (T1WI) in the culprit plaque [hazard ratio (HR) =3.798, 95% CI: 1.433 to 10.062] was an independent risk factor for stroke recurrence. The incidence of significant enhancement (62.2% 39.5%, χ=9.681, P=0.002), positive remodeling (69.5% 52.4%, χ=5.661, P=0.020), and hyperintensity on T1WI (42.7% 22.6%, χ=16.472, P=0.003) was higher in the posterior circulation than in the anterior circulation.

Conclusions: The characteristics of intracranial arterial culprit plaques were independent risk factors for recurrent stroke, and there were differences in the plaque characteristics of anterior and posterior circulation. Early HR-VWI examination for sICAS patients is of great significance for patient risk stratification and personalized management.
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http://dx.doi.org/10.21037/atm-22-2586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279796PMC
June 2022

The Immune Change of the Lung and Bowel in an Ulcerative Colitis Rat Model and the Protective Effect of Sodium Houttuyfonate Combined With Matrine.

Front Immunol 2022 30;13:888918. Epub 2022 Jun 30.

Department of Emergency, the Affiliated Wuxi NO 2 People's Hospital of Nanjing Medical University, Wuxi, China.

Objective: To explore the immune change of lung injury of Ulcerative colitis (UC) by observing the changes of inherent immunity and adaptive immunity of the lung and bowel in UC rat models after the treatment of Sodium Houttuyfonate combined with Matrine.

Method: UC rat models were established with the mucous membrane of colon allergize combined with TNBS-alcohol enteroclysis for 1 week and 5 weeks. 1-week experimental rats were divided into normal group and model group, 5/each group. 5-weeks experimental rats were divided into normal group, model group, Sodium Houttuyfonate (2.9mg/ml) combined with Matrine (1.47mg/ml), and positive control sulfasalazine (10mg/ml), 5/each group. All rats were administered by gavage for 5 weeks. The histopathological and fibrotic changes in the lung and bowel were observed, and the expressions of Tumor Necrosis Factor (TNF)- α, interleukin (IL)-8 in the lung, bowel, and serum were detected by radio-immunity and immunohistochemistry, and the mRNA expressions of Toll-like receptor (TLR)-4, nuclear factor kappa (NF-κB), Macrophage migration inhibitory factor (MIF), Mucosal addressing cell adhesion molecule-1 (MadCAM1) and Pulmonary surfactant protein-A (SP-A) in the lung and bowel were detected by Real time-PCR.

Result: Compared with the normal group, the model rats had significant histopathological and fibrotic changes both in the lung and bowel, and all treatment groups were improved. After treatment, TLR4, IL-8, MIF, and TNF-α in the lung decreased (P<0.05); NF-KB, IL-8, and MIF in the bowel increased (P<0.05); MadCAM1 both in lung and bowel decreased (P<0.05); SP-A decreased in bowel and increased in the lung (P<0.05).

Conclusion: The cause of lung injury in this model was found to be related to inherent immunity and adaptive immunity, while the cause of bowel injury in this model was found to be mainly related to adaptive immunity. Sodium Houttuyfonate combined with Matrine could improve bowel and lung injury.
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http://dx.doi.org/10.3389/fimmu.2022.888918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280623PMC
June 2022

Chromosome-level assembly and analysis of the Thymus genome provide insights on glandular secretory trichome formation and monoterpenoid biosynthesis in thyme.

Plant Commun 2022 Jul 15:100413. Epub 2022 Jul 15.

Key Laboratory of Plant Resources and Beijing Botanical Garden, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China. Electronic address:

Thyme has medicinal and aromatic value because of its potent antimicrobial and antioxidant properties. However, the absence of a fully sequenced thyme genome limits functional genomic studies in Chinese native thymes. Thymus quinquecostatus Celak., which contains large amounts of bioactive monoterpenes, such as thymol and carvacrol, is an important wild medicinal and aromatic plant in China. Monoterpenoids are abundant in glandular secretory trichomes. Here, high-fidelity and chromatin conformation capture technologies were used to assemble and annotate the T. quinquecostatus genome at the chromosome level. The 13 chromosomes of T. quinquecostatus had a total length of 528.66 megabases (Mb), a contig N50 of 8.06 Mb, and BUSCO of 97.34%. We found that T. quinquecostatus experienced two whole-genome duplications, with the most recent event occurring ∼4.34 million years ago. Deep analyses of the genome, in conjunction with comparative genomic, phylogenetic, transcriptomic, and metabonomic studies, uncovered many regulatory factors and genes related to monoterpenoids and glandular secretory trichome development. Terpene synthase (TPS)-, cytochrome P450 monooxygenases (CYP)-, short-chain dehydrogenase/reductase (SDR)-, R2R3-MYB-, and homeodomain-leucine zipper (HD-ZIP) IV-encoding genes were among those present in the T. quinquecostatus genome. Notably, Tq02G002290.1 (TqTPS1) was shown to be the gene encoding the terpene synthase responsible for catalyzing geranyl diphosphate (GPP) to produce the main monoterpene product γ-terpinene. Our study provides significant insight into the mechanism of glandular secretory trichome formation and monoterpenoid biosynthesis in thyme. Furthermore, this work will facilitate the development of molecular breeding tools to enhance the productivity of bioactive secondary metabolites in Lamiaceae.
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http://dx.doi.org/10.1016/j.xplc.2022.100413DOI Listing
July 2022

Mid-aortic syndrome: a rare cause of heart failure in infants.

ESC Heart Fail 2022 Jul 11. Epub 2022 Jul 11.

Cardiovascular Center, Children's Hospital of Fudan University, Shanghai, 201102, China.

This case reports describe a rare disease, mid-aortic syndrome (MAS), that can cause severe heart failure and hypertension in infancy. The typical images, key points of diagnosis, and therapy methods of the disease have also been presented. We report two critical thoracoabdominal aortic coarctation cases in infants aged 2 and 11 months with severe heart failure. The patients were initially misdiagnosed as dilated myocardiopathy, with the correct diagnosis confirmed through imaging. Both patients underwent balloon angioplasty; one patient also had bare-metal stents implanted. The patient treated with balloon angioplasty alone died after the procedure, whereas the other patient recovered well. In conclusion, careful physical examinations, especially upper and lower extremity blood pressure differences and palpation of upper and lower limb pulses, are critical in unexplained infant heart failure cases. Stent implantation may be a safer and more effective treatment than simple balloon angioplasty in infants with MAS.
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http://dx.doi.org/10.1002/ehf2.14066DOI Listing
July 2022

The Experimental Exploration of TCM Theory "Treating the Same Disease with Different Approaches" on an Ulcerative Colitis Model.

Evid Based Complement Alternat Med 2022 30;2022:4916540. Epub 2022 Jun 30.

Department of Internal Medicine of TCM, Nantong Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nantong, Jiangsu 226000, China.

There is a relationship between lung injury and ulcerative colitis. Currently, traditional Chinese medicine (Huangqi Jiegeng (HQJGD) and Huangqi Huanglian decoctions (HQHLD)) is commonly used for UC-related lung injury; however, the mechanisms of these drugs remain unclear. In this study, UC models were established with the mucous membrane of colon allergize combined with TNBS-alcohol enteroclysis for 4 weeks. The pathological changes in the lung, intestine, liver, and kidney were observed; cytokines, chemokines, and adhesion molecules in lung tissue were detected in order to explore the immunological mechanism of UC-related lung injury and the intervention mechanism of traditional Chinese medicine in treating the lung and intestine in the immune-TNBS-ethanol rat model. Histology examinations demonstrated evident pathological changes in the lungs and intestines of the model groups. Furthermore, all groups treated with TCMs demonstrated reduced expressions of toll-like receptor 4, nuclear factor kappa-B, and macrophage migration inhibitory factor. Additionally, radioimmunoassay and immunohistochemistry showed tumor necrosis factor-, interleukin-6, and 8 expression downregulation. The results showed that HQJGD and HQHLD could alleviate pulmonary inflammation in UC-related lung injury by obviously improving the pathology and fibrosis of the lung, inhibiting the positive feedback loop of MIF/NF-B, and reducing lymphocyte homing to bronchial mucosa. This model revealed the immune mechanism of UC-related lung injury and the intervention mechanism of the Chinese medicine, which provided the rationale for treating ulcerative colitis clinically, so as to demonstrate the theory of "the lung and the large intestine being interior-exteriorly related" and "treating the same disease with different approaches."
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http://dx.doi.org/10.1155/2022/4916540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262511PMC
June 2022

Emulsifying properties and bioavailability of clove essential oil Pickering emulsions stabilized by octadecylaminated carboxymethyl curdlan.

Int J Biol Macromol 2022 Jul 8;216:629-642. Epub 2022 Jul 8.

Key Laboratory of Carbohydrate Chemistry and Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu 214122, China. Electronic address:

In the present study, clove essential oil (CEO) Pickering emulsions were stabilized by octadecylamine-modified carboxymethyl curdlan (CMCD-ODA) at different pH values. The droplet size and negatively charged zeta potential of the CMCD-ODA emulsions decreased as the pH increased from 3.0 to 11.0. Rheology results indicated that the CMCD-ODA polymer/emulsion prepared at pH 5.0 showed higher apparent viscosity and viscoelasticity than other pH conditions, which might prevent droplets from flocculating. The Pickering emulsions obtained at pH 5.0 were spherical droplets with a uniform size distribution and a mean diameter of 9.54 μm, and they exhibited excellent stability during 28 days of storage. The morphological structures of the emulsions investigated by confocal laser scanning microscopy and scanning electron microscopy indicated that the CMCD-ODA Pickering emulsion obtained at pH 5.0 was stabilized by loading amphiphilic CMCD-ODA polymer around the spherical oil droplets and forming a weak gel network structure. The CEO-loaded CMCD-ODA emulsions had higher antioxidant capacity than free CEO after 28 days of storage at pH 5.0. Given the good emulsion stability, antioxidant activity, and great antibacterial effect, the CEO-loaded carboxymethyl curdlan Pickering emulsion has promising applications in food, cosmetic, and biomedicine industries.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.07.029DOI Listing
July 2022
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