Publications by authors named "Lihua Chen"

335 Publications

Effect of the Notch4/Dll4 signaling pathway in early gestational intrauterine infection on lung development.

Exp Ther Med 2021 Sep 8;22(3):972. Epub 2021 Jul 8.

Department of Neonatology, Children's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.

Intrauterine infection is an important risk factor for bronchopulmonary dysplasia (BPD). BPD is characterized by arrested lung alveolarization and impaired pulmonary vascularization. The Notch4 signaling pathway is a key regulator of vascular remodeling and angiogenesis. Therefore, the presents study investigated the expression of Notch4, delta-like canonical Notch ligand 4 (Dll4) and related factors in an rat model and in rat pulmonary microvascular endothelial cells (PMVECs) , to study the mechanisms by which intrauterine infection affects rat lung development. A rat model of intrauterine infection was established by endocervical inoculation with on embryonic day 15. The date of birth was counted as postnatal day 0 (P0). Then, the lung tissues were collected from pups at days P3-P14. The expression of Notch4, Dll4 and related factors was measured by reverse transcription-quantitative PCR and western blotting. In addition, the γ-secretase inhibitor DAPT was used to examine the effect of Notch4 signaling on PMVECs. Intrauterine infection impaired normal lung development, as indicated by decreased microvessel density, fewer alveoli, fewer secondary septa, and larger alveoli compared with the control group. Furthermore, Notch4, Dll4 and NF-κB levels were significantly increased in the -infected group at P3 compared with the control group. Similarly, the mRNA expression levels of fetal liver kinase 1 (Flk-1, a VEGF receptor) were significantly increased in the -infected group at P3 and P7. In PMVECs, the inhibition of Notch4 signaling contributed to decreases in lipopolysaccharide (LPS)-induced expression of VEGF and its receptors. Furthermore, the inhibition of Notch4/Dll4 signaling accelerated cell proliferation and decreased the apoptosis rate of LPS-induced PMVECs. LPS-induced NF-κB expression in PMVECs was also attenuated by the Notch4/Dll4 inhibitor. In conclusion, intrauterine infection impaired normal lung development, possibly through Notch4/Dll4 signaling and effects on VEGF and its receptors.
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http://dx.doi.org/10.3892/etm.2021.10404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290428PMC
September 2021

The School-Ladder Effect: Subjective Socioeconomic Status and Diurnal Cortisol Profile among Adolescents.

Psychosom Med 2021 Jul 7. Epub 2021 Jul 7.

Department of Psychology, University of Macau, Macau SAR, China Institute of Advanced Studies in Humanities and Social Sciences, Beijing Normal University at Zhuhai, Zhuhai, China Department of Psychology, Wayne State University, Detroit, MI, United States Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, MI, United States Department of Psychology, Guangzhou University, Guangzhou, China Center for Cognitive and Brain Sciences, University of Macau, Macau SAR, China.

Objective: Subjective socioeconomic status (SES) is a well-established psychosocial determinant of adolescents' self-report health. However, whether low subjective SES is associated with stress-related physiological risks (e.g., dysregulations in the hypothalamic-pituitary-adrenocortical axis activity) remains uncertain. This study examined the impacts of subjective SES with different reference groups (i.e., perception of family SES relative to other students in the school versus other people in the city) on adolescents' diurnal cortisol profiles.

Methods: A sample of 255 adolescents (aged 11-14; 53.7% boys) completed a battery of psychological scales, including school-referenced subjective SES and city-referenced subjective SES. Diurnal cortisol was assessed by collecting saliva samples four times a day across two consecutive days. Four cortisol parameters (cortisol at awakening, cortisol awakening response [CAR], cortisol slope, and total cortisol secretion [AUCg]) were derived.

Results: Higher levels of school-referenced subjective SES were associated with higher cortisol levels at awakening (β = 0.0483, SE = 0.0219, p = 0.028), steeper cortisol slopes (β = -0.0036, SE = 0.0017, p = 0.034), and higher cortisol AUCg (b = 0.50, SE = 0.24, p = 0.036), but not with CAR (p = 0.77), after adjusting for covariates. In contrast, city-referenced subjective SES was not associated with any of the cortisol parameters (cortisol at awakening [p = 0.90], CAR [p = 0.74], cortisol slope [p = 0.84], and cortisol AUCg [p = 0.68]).

Conclusions: Our findings highlight the importance of the reference group for subjective SES and provide a further understanding of socioeconomic disparities in adolescents' stress physiology.
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http://dx.doi.org/10.1097/PSY.0000000000000974DOI Listing
July 2021

Novel high voltage polymer insulators using computational and data-driven techniques.

J Chem Phys 2021 May;154(17):174906

School of Materials Science and Engineering, Georgia Institute of Technology, 771 Ferst Drive NW, Atlanta, Georgia 30332, USA.

One of the key bottlenecks in the development of high voltage electrical systems is the identification of suitable insulating materials capable of supporting high voltages. Under high voltage scenarios, conventional polymer based insulators, which are one of the popular choices of insulators, suffer from the drawback of space charge accumulation, which leads to degradation in desirable electronic properties and facilitates dielectric breakdown. In this work, we aid the development of novel polymers for high voltage insulation applications by enabling the rapid prediction of properties that are correlated with dielectric breakdown, i.e.,the bandgap (E) of the polymer and electron injection barrier (Φ) at the electrode-insulator interface. To accomplish this, density functional theory based methods are used to develop large, chemically diverse datasets of Φ and E. The deviation of the computed properties from experimental observations is addressed using a statistical technique called Bayesian calibration. Furthermore, to enable rapid estimation of these properties for a large set of polymers, machine learning models are developed using the created dataset. These models are further used to predict E and Φ for a set of 13k previously known polymers. Polymers with high values of these properties are selected as potential high voltage insulators and are recommended for synthesis. Finally, the models developed here are deployed at www.polymergenome.org to enable the community use.
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http://dx.doi.org/10.1063/5.0044306DOI Listing
May 2021

The Neurogenic Compound P7C3 Regulates the Aerobic Glycolysis by Targeting Phosphoglycerate Kinase 1 in Glioma.

Front Oncol 2021 18;11:644492. Epub 2021 Jun 18.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.

Background: P7C3 is a neurogenic compound that exhibits neuroprotective properties in neural cells. However, its target proteins and effects in glioma are unknown.

Methods: The candidate P7C3 target proteins were analyzed using a human protein microarray containing 23136 human proteins. A streptavidin agarose affinity assay was used to verify the direct interaction between P7C3 and phosphoglycerate kinase 1 (PGK1). Mass spectrometry was used to identify the binding sites of PGK1 for P7C3 binding. Seahorse XF96 extracellular flux analyzer was used to measure the cell oxygen consumption rate and extracellular acidification rate. Glycolytic metabolites were measured using the related kits. Protein level was detected by western blotting and immunohistochemical staining. Autophagy was analyzed using a transmission electron microscope and western blotting. The malignancy of tumor progression and was analyzed based on cell viability, apoptosis and proliferation, migration and invasion, and xenograft model. Glial cells were marked by antibodies immunohistochemical staining.

Results: The human protein microarray identified 577 candidate P7C3 target proteins. The global profile of P7C3 target proteins indicated that P7C3 regulates glycolysis. Metabolic experiments confirmed that P7C3 regulates aerobic glycolysis in glioma cells. The underlying mechanism of P7C3 was found to be direct targeting PGK1 at lysine residues and asparagine residues, and the specific P7C3-PGK1 interaction led to decreased protein level and total intracellular kinase activity of PGK1. The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases indicated that the mRNA level of PGK1 is significantly increased in high-grade glioma, and the abnormally high mRNA level of PGK1 is associated with a poor prognosis in patients with glioma, suggesting that PGK1 is a promising target for glioma therapy. The inhibition of PGK1 and the subsequent suppression of aerobic glycolysis caused by P7C3 inhibited the malignant growth of glioma and . Furthermore, P7C3 did not damage normal glial cells under concentration, which exhibit an inhibitory effect on gliomas.

Conclusions: This study revealed that P7C3 suppresses glioma by regulating aerobic glycolysis directly targeting PGK1. Furthermore, we identified the P7C3 target proteins for the first time which is expected to provide scientific clues for future studies.
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http://dx.doi.org/10.3389/fonc.2021.644492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252887PMC
June 2021

Identification of Somatic Genetic Alterations Using Whole-Exome Sequencing of Uterine Leiomyosarcoma Tumors.

Front Oncol 2021 11;11:687899. Epub 2021 Jun 11.

Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: The genomic abnormalities associated with uterine leiomyosarcoma (uLMS) have not been fully elucidated to date.

Objective: To understand the pathogenesis of uLMS and to identify driver mutations and potential therapeutic targets in uLMS.

Methods: Three matched tumor-constitutional DNA pairs from patients with recurrent uLMS were subjected to whole-exome capture and next-generation sequencing. The role of the selected gene in uLMS was analyzed by the CCK-8 assay and colony formation assay after specific siRNA knockdown.

Results: We identified four genes with somatic SNVs, namely, SLC39A7, GPR19, ZNF717, and TP53, that could be driver mutations. We observed that 30.7% (4/13) of patients with uLMS had TP53 mutations as analyzed by direct sequencing. Analysis of somatic copy number variants (CNVs) showed regions of chromosomal gain at 1q21-23, 19p13, 17q21, and 17q25, whereas regions of chromosomal loss were observed at 2q35, 2q37, 1p36, 10q26, 6p22, 8q24, 11p15, 11q12, and 9p21. The gene was amplified in two patients and mutated in another (: NM_030974: exon2: c.G264C, p.E88D). Amplification of the gene was associated with shorter PFS and OS in soft tissue sarcoma, as shown by TCGA database analysis. Knockdown of expression was observed to decrease cell growth and colony formation in uterine sarcoma cell lines.

Conclusions: Exome sequencing revealed mutational heterogeneity of uLMS. The gene was amplified in uLMS and could be a candidate oncogene.
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http://dx.doi.org/10.3389/fonc.2021.687899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226214PMC
June 2021

Corrigendum: Synergistic Microbicidal Effect of Auranofin and Antibiotics Against Planktonic and Biofilm-Encased and .

Front Microbiol 2021 4;12:694670. Epub 2021 Jun 4.

Department of Clinical Laboratory, The Third Xiangya Hospital of Central South University, Changsha, China.

[This corrects the article DOI: 10.3389/fmicb.2019.02453.].
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http://dx.doi.org/10.3389/fmicb.2021.694670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212051PMC
June 2021

The Use of Aerosolized Medications in Adult Intensive Care Unit Patients: A Prospective, Multicenter, Observational, Cohort Study.

J Aerosol Med Pulm Drug Deliv 2021 Jun 14. Epub 2021 Jun 14.

Department of Respiratory and Critical Care Medicine, West China Medical Center, Sichuan University, Chengdu, China.

Only limited data are available on the real-life clinical utilization of aerosolized medications in intensive care unit (ICU) patients. Exploring the utilization of aerosolized medications in the ICU may contribute to develop appropriate education and improve the quality of aerosol therapy. A 2-week, prospective, multicenter, observational, cohort study was conducted to record how the aerosolized medications were utilized in the Chinese ICUs, including indications, medications used in solo or combination, dosage, and side-effects in adult patients. A total of 1006 patients from 28 ICUs were enrolled, of which 389 (38.7%) received aerosol therapy. The most common indications for aerosol therapy were difficulty in secretion management (23.1%) and chronic obstructive pulmonary disease exacerbation (18.5%). The combination of inhaled corticosteroids and short-acting muscarinic antagonist was the most commonly used medication (19.5%, 76/389). Ninety-two percent (358/389) of the patients did not have any side effects during aerosol therapy. More patients in the group with mechanical ventilation received bronchodilators than spontaneous breathing patients (81.3% vs. 55.5%,  < 0.001), and more patients who breathed spontaneously through a tracheostomy received mucus-regulating agents than other patients (70% vs. 37.9%,  = 0.004). In mainland China, more than one-third of adult ICU patients received aerosol therapy. Medications utilized during aerosol therapy were variable in patients with different respiratory support. To promote appropriate use of aerosolized medications, high-quality randomized, controlled trials and clinical guidance on aerosolized medication indications and dosing are needed to improve clinical outcomes.
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http://dx.doi.org/10.1089/jamp.2021.0004DOI Listing
June 2021

An Informatics Approach for Designing Conducting Polymers.

ACS Appl Mater Interfaces 2021 May 26. Epub 2021 May 26.

Department of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.

Doping conjugated polymers, which are potential candidates for the next generation of organic electronics, is an effective strategy for manipulating their electrical conductivity. However, selecting a suitable polymer-dopant combination is exceptionally challenging because of the vastness of the chemical, configurational, and morphological spaces one needs to search. In this work, high-performance surrogate models, trained on available experimentally measured data, are developed to predict the p-type electrical conductivity and are used to screen a large candidate hypothetical data set of more than 800 000 polymer-dopant combinations. Promising candidates are identified for synthesis and device fabrication. Additionally, new design guidelines are extracted that verify and extend knowledge on important molecular fragments that correlate to high conductivity. Conductivity prediction models are also deployed at www.polymergenome.org for broader open-access community use.
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http://dx.doi.org/10.1021/acsami.1c04017DOI Listing
May 2021

Polymer informatics with multi-task learning.

Patterns (N Y) 2021 Apr 9;2(4):100238. Epub 2021 Apr 9.

School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.

Modern data-driven tools are transforming application-specific polymer development cycles. Surrogate models that can be trained to predict properties of polymers are becoming commonplace. Nevertheless, these models do not utilize the full breadth of the knowledge available in datasets, which are oftentimes sparse; inherent correlations between different property datasets are disregarded. Here, we demonstrate the potency of multi-task learning approaches that exploit such inherent correlations effectively. Data pertaining to 36 different properties of over 13,000 polymers are supplied to deep-learning multi-task architectures. Compared to conventional single-task learning models, the multi-task approach is accurate, efficient, scalable, and amenable to transfer learning as more data on the same or different properties become available. Moreover, these models are interpretable. Chemical rules, that explain how certain features control trends in property values, emerge from the present work, paving the way for the rational design of application specific polymers meeting desired property or performance objectives.
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http://dx.doi.org/10.1016/j.patter.2021.100238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085610PMC
April 2021

Tr1 Cells as a Key Regulator for Maintaining Immune Homeostasis in Transplantation.

Front Immunol 2021 26;12:671579. Epub 2021 Apr 26.

Department of Immunology, The Fourth Military Medical University, Xi'an, China.

The immune system is composed of effectors and regulators. Type 1 regulatory T (Tr1) cells are classified as a distinct subset of T cells, and they secret high levels of IL-10 but lack the expression of the forkhead box P3 (Foxp3). Tr1 cells act as key regulators in the immune network, and play a central role in maintaining immune homeostasis. The regulatory capacity of Tr1 cells depends on many mechanisms, including secretion of suppressive cytokines, cell-cell contacts, cytotoxicity and metabolic regulation. A breakdown of Tr1-cell-mediated tolerance is closely linked with the pathogenesis of various diseases. Based on this observation, Tr1-cell therapy has emerged as a successful treatment option for a number of human diseases. In this review, we describe an overview of Tr1 cell identification, functions and related molecular mechanisms. We also discuss the current protocols to induce/expand Tr1 cells for clinical application, and summarize the recent progress of Tr1 cells in transplantation.
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http://dx.doi.org/10.3389/fimmu.2021.671579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109434PMC
April 2021

Compositional and functional responses of bacterial community to titanium dioxide nanoparticles varied with soil heterogeneity and exposure duration.

Sci Total Environ 2021 Jun 4;773:144895. Epub 2021 Feb 4.

Institute of Environmental Sciences (CML), Leiden University, P.O. Box 9518, 2300 RA Leiden, the Netherlands.

Titanium dioxide nanoparticles (TiO NPs) are widely used as nano-agrochemicals. In this study we investigated the influence of soil heterogeneity on bacterial communities exposed to TiO NPs over time. Clay and sandy soils with low- and high-organic matter contents were exposed to environmentally relevant concentration of TiO NPs (1 mg/kg) and soil bacterial communities were sampled after short-term (15 days) and long-term exposure (60 days). After short-term TiO NPs exposure, significant effects regarding the enzyme activity, bacterial community structure and composition, and community functioning were observed in the clay soils with high organic matter (clay-HOM) but not in other soil groups. Response alterations were observed to taxa belonging to Acidobacteria and Verrucomicrobia, and functional pathways related to carbohydrates degradation. These results indicated that soil heterogeneity play more important roles in shaping the bacterial community in soil with low clay fraction and less organic matter, while TiO NPs selection was the main driver in inducing the compositional and functional impacts on the soil bacterial community in the presence of clay soil with high organic matter content. As exposure time increased, the bacterial community recovered after a long-term exposure of 60 days, suggesting that the bacterial evolution and adaptation could overcome the TiO NPs selection after long-term exposure. Our results highlighted the importance of soil heterogeneity including clay fraction and organic matter and exposure duration in assessing the impact of nanoparticle on soil bacterial activity, community and function. By comprehensively evaluating the risks of nanoparticles on soil ecosystem and explicitly and explicitly include spatial and temporal variations, the benefit of nano-agrochemical products has the potential to be promoted in future applications.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144895DOI Listing
June 2021

Isolation and characterization of neuroprotective lignans from salted Aconiti lateralis Radix Praeparata.

Biosci Biotechnol Biochem 2021 May;85(6):1448-1451

Key Laboratory of Modern Preparation of Traditional Chinese Medicine of Ministry of Education and Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China.

Six lignans (1-6) were isolated from salted Aconiti lateralis Radix Praeparata for the first time. These isolates were elucidated as hedyotisol-A (1), (7″R,8″R)-8″-syringaresinol-4″-hydroxy-3″,5″-dimethoxyphenyl-7″,9″-propanediol (2), lariciresinol-4-O-β-d-glucopyranoside (3),(7S,8S)-4-hydroxy-3-methoxy-7,8-(2',1'-O-β-d-glucopyranosyl)phenyl-propanetriol (4), (+)-isolariciresinol (5), and (+)-lyoniresinol (6) by analyzing extensive and comprehensive spectral data and compared with the data described in the literature, respectively. Compounds (1-6) were evaluated for their neuroprotective activities against corticosterone-induced cell death in PC12 cells with desipramine as the positive control drug. Among them, compounds 1 and 2 showed moderate neuroprotective activities, which increased the survival rates of PC12 cells from 45.50 ± 2.23% to 65.98 ± 1.29%, 58.19 ± 2.94% at 10 µm, respectively.
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http://dx.doi.org/10.1093/bbb/zbab067DOI Listing
May 2021

Functional disability and post-traumatic stress disorder in survivors of mechanical ventilation: a cross-sectional study in Guangzhou, China.

J Thorac Dis 2021 Mar;13(3):1564-1575

Department of Critical Care Medicine, Guangzhou Institute of Respiratory Health, The 1st Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Critical illness is associated with cognitive, physical, and psychological impairments; however, evidence of the severity and frequency of impairments in Chinese survivors of mechanical ventilation in an intensive care unit (ICU) remains limited. Our aim was to investigate the incidence and severity of impairments in Chinese survivors of mechanical ventilation in ICU and to explore risk factors influencing specific impairments.

Methods: Patients discharged alive after mechanical ventilation in a large general ICU for ≥2 days were enrolled in this single-center cross-sectional study. Survivors were evaluated using measures of functional disability (Activity of Daily Living Scale), and post-traumatic stress disorder (PTSD, The Impact of Event Scale-Revised) via telephone interview. Multivariable analysis was conducted.

Results: Data were obtained from 130 consenting survivors. At follow-up (mean: 19.64 months), among those in part-time or full-time employment prior to admission, only 45.1% had returned to work. Further, 29.2% of survivors had clear disabilities affecting daily living. Deficits in activities of daily living (ADL) were mainly characterized by impairment of instrumental ADL. Predictors of ADL in mechanically ventilated survivors included age, ICU admission diagnosis, and Acute Physiology And Chronic Health Evaluation II (APACHE II) score, which accounted for 33.5% of total variance. Furthermore, 17.7% of participants had symptoms consistent with PTSD. ICU length of stay was the only predictor of PTSD, and accounted for 7.5% of total variance.

Conclusions: ICU survivors of mechanical ventilation in China face negative impacts on employment, and commonly have ADL impairment and PTSD. Age, ICU admission diagnosis, and APACHE II score were key factors influencing ADL, while ICU length of stay was the only factor affecting PTSD. These findings suggest that some survivors who have had certain exposures may warrant closer follow-up, and systematic interventions for these high-risk survivors should be developed in China.
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http://dx.doi.org/10.21037/jtd-20-2622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024792PMC
March 2021

Determination of Toxic Pyrrolizidine Alkaloids in Traditional Chinese Herbal Medicines by UPLC-MS/MS and Accompanying Risk Assessment for Human Health.

Molecules 2021 Mar 16;26(6). Epub 2021 Mar 16.

The Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.

Pyrrolizidine alkaloids (PAs) are a class of natural toxins with hepatotoxicity, genotoxicity and carcinogenicity. They are endogenous and adulterated toxic components widely found in food and herbal products. In this study, a sensitive and efficient ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was used to detect the PAs in 386 kinds of Chinese herbal medicines recorded in the Chinese Pharmacopoeia (2020). The estimated daily intake (EDI) of 0.007 μg/kg body weight (bw)/day was adopted as the safety baseline. The margin of exposure (MOE) approach was applied to evaluate the chronic exposure risk for the genotoxic and carcinogenic potential of PAs. Results showed that PAs was detected in 271 out of 386 samples with a content of 0.1-25,567.4 μg/kg, and there were 20 samples with EDI values above the baseline, 0.007 μg/kg bw/day. Beyond that, the MOE values for 10 out of 271 positive samples were below 10,000. Considering the actual situation, Haber's rule was used to assume two weeks exposure every year during lifetime, and still the MOE values for four out of 271 positive samples were under 10,000, indicating these products may have potential health risk. The developed method was successfully applied to detect the PAs-containing Chinese herbal medicines. This study provides convincing data that can support risk management actions in China and a meaningful reference for the rational and safe use of Chinese herbal medicines.
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http://dx.doi.org/10.3390/molecules26061648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000276PMC
March 2021

Neonatal Ureaplasma parvum meningitis complicated with subdural hematoma: a case report and literature review.

BMC Infect Dis 2021 Mar 17;21(1):268. Epub 2021 Mar 17.

Departments of Neonatology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

Background: Neonatal meningitis is a severe infectious disease of the central nervous system with high morbidity and mortality. Ureaplasma parvum is extremely rare in neonatal central nervous system infection.

Case Presentation: We herein report a case of U. parvum meningitis in a full-term neonate who presented with fever and seizure complicated with subdural hematoma. After hematoma evacuation, the seizure disappeared, though the fever remained. Cerebrospinal fluid (CSF) analysis showed inflammation with CSF pleocytosis (1135-1319 leukocytes/μl, mainly lymphocytes), elevated CSF protein levels (1.36-2.259 g/l) and decreased CSF glucose (0.45-1.21 mmol/l). However, no bacterial or viral pathogens in either CSF or blood were detected by routine culture or serology. Additionally, PCR for enteroviruses and herpes simplex virus was negative. Furthermore, the CSF findings did not improve with empirical antibiotics, and the baby experienced repeated fever. Thus, we performed metagenomic next-generation sequencing (mNGS) to identify the etiology of the infection. U. parvum was identified by mNGS in CSF samples and confirmed by culture incubation on mycoplasma identification medium. The patient's condition improved after treatment with erythromycin for approximately 5 weeks.

Conclusions: Considering the difficulty of etiological diagnosis in neonatal U. parvum meningitis, mNGS might offer a new strategy for diagnosing neurological infections.
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http://dx.doi.org/10.1186/s12879-021-05968-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968305PMC
March 2021

Safety of high-dose in adolescent rats based on metabolomics.

Food Sci Nutr 2021 Feb 1;9(2):794-810. Epub 2020 Dec 1.

Jiangxi University of Traditional Chinese Medicine Nanchang China.

is the dried root of the leguminous plant and is a common component of health products and medicines. Although it is considered safe, some studies have reported that has hepatotoxicity and estrogen-like effects. In this study, the safety of high doses of water extract administered to adolescent rats for 30 days was evaluated by biochemical, histopathological, and metabolomic analyses. Overall, there were no significant differences between the low-dose and blank control groups in parameter values, including organ wet weight, organ coefficient, routine blood indicators, serum biochemical indexes of liver and renal function, levels of estradiol and testosterone, histopathological parameters, and primary differential metabolite profiles. Compared with the blank control group, the high-dose group may have a certain effect on the liver. These effects might be mediated by abnormal phenylalanine, tyrosine, and tryptophan biosynthesis or phenylalanine metabolism. However, histopathological analyses did not show differences in the liver, kidney, breast, uterus, ovary, testis, and epididymis between the control group and the group treated with a high dose of water extract. water extract did not significantly promote the precocity of male and female sexual organs. Overall, water extract is relatively safe for adolescent rats.
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http://dx.doi.org/10.1002/fsn3.2044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866568PMC
February 2021

Triumeq Increases Excitability of Pyramidal Neurons in the Medial Prefrontal Cortex by Facilitating Voltage-Gated Ca Channel Function.

Front Pharmacol 2020 28;11:617149. Epub 2021 Jan 28.

Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL, United States.

Combination antiretroviral therapy (cART) suppresses HIV-1 replication, improves immune function, and prolongs the life of people living with HIV (PLWH). However, cART also induces neurotoxicity that could complicate HIV-induced neurodegeneration while reduce its therapeutic efficacy in treating HIV/AIDS. Triumeq is a first-line cART regimen, which is co-formulated by three antiretroviral drugs (ARVs), lamivudine (3TC), abcavir (ABC), and dolutegravir (DTG). Little is known about potential side effects of ARVs on the brain (including those co-formulating Triumeq), and their mechanisms impacting neuronal activity. We assessed acute () and chronic () effects of Triumeq and co-formulating ARVs on pyramidal neurons in rat brain slices containing the medial prefrontal cortex (mPFC) using patch-clamp recording approaches. We found that acute Triumeq or 3TC significantly increased firing of mPFC neurons in a concentration- and time-dependent manner. This neuronal hyperactivity was associated with enhanced Ca influx through voltage-gated Ca channels (VGCCs). Additionally, chronic treatment with Triumeq for 4 weeks (4 wks) also significantly increased firing and Ca influx via VGCCs in mPFC neurons, which was not shown after 2 wks treatment. Such mPFC neuronal hyperexcitability was not found after 4 weeks treatments of individual ARVs. Further, chronic Triumeq exposure significantly enhanced mRNA expression of low voltage-activated (LVA) L-type Ca channels (Ca1.3 L-channels), while changes in high voltage-activated (HVA) Cav1.2 L-channels were not observed. Collectively, these novel findings demonstrate that chronic cART induces hyperexcitability of mPFC pyramidal neurons by abnormally promoting VGCC overactivation/overexpression of VGCCs (including, but may not limited to, LVA-Ca1.3 L-channels), which could complicate HIV-induced neurotoxicity, and ultimately may contribute to HIV-associated neurocognitive disorders (HAND) in PLWH. Determining additional target(s) of cART in mPFC pyramidal neurons may help to improve the therapeutic strategies by minimizing the side effects of cART for treating HIV/AIDS.
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http://dx.doi.org/10.3389/fphar.2020.617149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876243PMC
January 2021

Induced neural stem cell grafts exert neuroprotection through an interaction between Crry and Akt in a mouse model of closed head injury.

Stem Cell Res Ther 2021 02 12;12(1):128. Epub 2021 Feb 12.

Department of Neurosurgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.

Background: Recently, growing evidence has indicated an important role of the complement system, a crucial component of immunity, in mediating neuroinflammation and promoting neuronal apoptosis following closed head injury (CHI). We previously reported that transplanted induced neural stem cells (iNSCs) pre-treated with CHI mouse serum could enhance complement receptor type 1-related protein y (Crry) expression and ameliorate complement-mediated damage in mouse CHI models. However, the mechanism underlying the elevated levels of Crry expression remains elusive.

Methods: CHI models were established using a standardized weight-drop device. We collected CHI mouse serum at 12 h post-trauma. RT-QPCR assay, western blot analysis, complement deposition assay, Akt inhibition assay, flow cytometry, cell transplantation, and functional assay were utilized to clarify the mechanism of Crry expression in iNSCs receiving CHI mouse serum treatment.

Results: We observed dramatic increases in the levels of Crry expression and Akt activation in iNSCs receiving CHI mouse serum treatment. Remarkably, Akt inhibition led to the reduction of Crry expression in iNSCs. Intriguingly, the treatment of iNSC-derived neurons with recombinant complement receptor 2-conjugated Crry (CR2-Crry), which inhibits all complement pathways, substantially enhanced Crry expression and Akt activation in neurons after CHI mouse serum treatment. In subsequent in vitro experiments of pre-treatment of iNSCs with CR2-Crry, we observed significant increases in the levels of Crry expression and Akt activation in iNSCs and iNSC-derived astrocytes and neurons post-treatment with CHI mouse serum. Additionally, an in vivo study showed that intracerebral-transplanted iNSCs pre-treated with CR2-Crry markedly enhanced Crry expression in neurons and protected neurons from complement-dependent damage in the brains of CHI mice.

Conclusion: INSCs receiving CR2-Crry pre-treatment increased the levels of Crry expression in iNSCs and iNSC-derived astrocytes and neurons and attenuated complement-mediated injury following CHI.
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http://dx.doi.org/10.1186/s13287-021-02186-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881465PMC
February 2021

Analysis of microbiomes in three traditional starters and volatile components of the Chinese rice wines.

Food Sci Biotechnol 2021 Jan 18;30(1):87-96. Epub 2020 Nov 18.

School of Perfume and Aroma Technology, Shanghai Institute of Technology, Fengxian District, 201418 Shanghai China.

To understand the effect of microbial community on the flavor of fermented rice wine, microbiomes in three traditional starters (CMQ, NBQ, and YCQ) from different origins for making Chinese rice wines were evaluated and the volatile components of their rice wines were compared. The results showed that the dominant genera in CMQ were , , , and , the dominant microorganisms in NBQ were , , , , , , and , the dominant microorganisms in YCQ were , , , , , , and . There were significant differences in sensory properties of the wines brewed by three starters. Although the major aroma components were benzyl alcohol, 2-octanone, benzoic acid, and phenethyl acetate, each rice wine had its own main aroma components include 1-octanol, 1-pentanol, ethyl acetate, etc. The results showed that the different microbial communities in starter results in the significant difference of the aroma components in its fermented rice wine.
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http://dx.doi.org/10.1007/s10068-020-00839-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847476PMC
January 2021

Association between serum netrin-1 and prognosis of ischemic stroke: The role of lipid component levels.

Nutr Metab Cardiovasc Dis 2021 03 12;31(3):852-859. Epub 2020 Nov 12.

Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA; Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.

Background And Aims: High serum netrin-1 levels decrease the risk of ischemic stroke and are negatively associated with outcomes after ischemic stroke. However, it remains unclear whether the association between netrin-1 and ischemic stroke prognosis is modified by lipid component levels.

Methods And Results: We measured baseline serum netrin-1 levels in 3065 ischemic stroke patients from China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a combination of death and major disability (modified Rankin Scale score≥3) at 3 months after ischemic stroke. Total cholesterol (TC) levels could modify the association between netrin-1 and prognosis of ischemic stroke (P = 0.040). After multivariate adjustment, the odds ratios of the primary outcome associated with the highest quartile of netrin-1 were 0.39 (95%CI, 0.17-0.90; P = 0.004) for the patients with high TC levels and 0.82 (95%CI, 0.61-1.11; P = 0.149) for those with normal TC levels. Adding netrin-1 to conventional risk factors improved risk prediction for the primary outcome in the patients with high TC levels (net reclassification improvement: 26.8%, P = 0.015; integrated discrimination index: 1.6%, P = 0.028) but not in those with normal TC levels.

Conclusions: Elevated netrin-1 is associated with improved prognosis at 3 months after ischemic stroke in the patients with high TC levels but not in those with normal TC levels. Further prospective studies from other populations and randomized clinical trials are needed to verify our findings and clarify the potential mechanisms.
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http://dx.doi.org/10.1016/j.numecd.2020.11.004DOI Listing
March 2021

PHB2 promotes tumorigenesis RACK1 in non-small cell lung cancer.

Theranostics 2021 1;11(7):3150-3166. Epub 2021 Jan 1.

Department of Respiratory and Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.

Lung cancer has the highest mortality rate among cancers worldwide, with non-small cell lung cancer (NSCLC) the most common type. Increasing evidence shows that PHB2 is highly expressed in other cancer types; however, the effects of PHB2 in NSCLC are currently poorly understood. PHB2 expression and its clinical relevance in NSCLC tumor tissues were analyzed using a tissue microarray. The biological role of PHB2 in NSCLC was investigated in vitro and in vivo using immunohistochemistry and immunofluorescence staining, gene expression knockdown and overexpression, cell proliferation assay, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, wound healing assay, Transwell assay, western blot analysis, qRT-PCR, coimmunoprecipitation, and mass spectrometry analysis. Our major finding is that PHB2 facilitates tumorigenesis in NSCLC by interacting with and stabilizing RACK1, which further induces activation of downstream tumor-promoting effectors. PHB2 was found to be overexpressed in NSCLC tumor tissues, and its expression was correlated with clinicopathological features. Furthermore, PHB2 overexpression promoted proliferation, migration, and invasion, whereas PHB2 knockdown enhanced apoptosis in NSCLC cells. The stimulating effect of PHB2 on tumorigenesis was also verified in vivo. In addition, PHB2 interacted with RACK1 and increased its expression through posttranslational modification, which further induced activation of the Akt and FAK pathways. Our results reveal the effects of PHB2 on tumorigenesis and its regulation of RACK1 and RACK1-associated proteins and downstream signaling in NSCLC. We believe that the crosstalk between PHB2 and RACK1 provides us with a great opportunity to design and develop novel therapeutic strategies for NSCLC.
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http://dx.doi.org/10.7150/thno.52848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847695PMC
July 2021

Effects of simultaneous and sequential cofermentation of and on physicochemical and flavor properties of rice wine.

Food Sci Nutr 2021 Jan 26;9(1):71-86. Epub 2020 Nov 26.

School of Perfume and Aroma Technology Shanghai Institute of Technology Shanghai China.

Microorganism species and inoculation fermentation methods have great influence on physicochemical and flavor properties of rice wine. Thus, this work investigated microbial interactions and physicochemical and aroma changes of rice wine through different inoculation strategies of and (. The results underlined that inoculation strategies and yeasts all affected the volatile acidity, total acidity, and alcohol content of rice wine. The sequential cofermentation consumed relatively more sugar and resulted in the higher ethanol content, causing reduced thiols and increased alcohols, esters, phenylethyls, and terpenes, which was more conducive to improve rice wine flavor than simultaneous cofermentation. Moreover, simultaneous cofermentation increased fatty aroma of rice wine, while sequential cofermentation increased mellow and cereal-like flavor. These results confirmed that sequential cofermentation of and was a choice for the future production of rice wine with good flavor and quality.
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http://dx.doi.org/10.1002/fsn3.1899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802529PMC
January 2021

CD226 deficiency attenuates the homeostasis and suppressive capacity of Tr1 cells.

Mol Immunol 2021 04 13;132:192-198. Epub 2021 Jan 13.

Department of Immunology, the Fourth Military Medical University, Xi'an 710032, China; Faculty of Medicine, Northwest University, Xi'an 710069, China. Electronic address:

T regulatory type 1 (Tr1) cells act as a key regulator in maintaining peripheral immune tolerance. Several costimulatory molecules for T cells have been identified in Tr1 cells, but their intrinsic functions are still unclear. Here we showed CD226 was highly expressed in Tr1 cells. CD226-deficient Tr1 cells were defective in proliferation and sensitive to apoptosis. In addition, CD226-deficient Tr1 cells showed lower inhibitory capacity of T cell proliferation and reduced IL-10 production. CD226 deficiency also inhibited Tr1 cell differentiation in vitro. When stimulated with IL-2, CD226-deficient Tr1 cells showed impaired STAT5 signaling. Therefore, our data suggest CD226 might play an important role in Tr1 cell homeostasis, function and differentiation. This study facilitates further biological characterization of this regulatory T cell subset.
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http://dx.doi.org/10.1016/j.molimm.2021.01.002DOI Listing
April 2021

Why Is the Invasive Plant More Resistant to High Temperature than Its Native Congener?

Int J Mol Sci 2021 Jan 13;22(2). Epub 2021 Jan 13.

Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Key Laboratory of Biotechnology for Plant Development, College of Life Sciences, South China Normal University, Guangzhou 510631, China.

Climate change and invasive alien species threaten biodiversity. High temperature is a worrying ecological factor. Most responses of invasive plants aimed at coping with adversity are focused on the physiological level. To explore the molecular mechanisms underlying the response of an invasive plant ( L.) to high temperature, using a native species ( L.) as the control, relevant indicators, including photosynthetic pigments, gas exchange, chlorophyll fluorescence, the antioxidant system, and related enzyme-coding genes were measured. The results showed that the leaves of turned yellow, photosynthetic pigment content (Chl , Chl , Car, Chl) decreased, gas exchange (P) and chlorophyll fluorescence parameters (F/F, Φ) decreased under high temperature. It was also found that high temperature caused photoinhibition and a large amount of ROS accumulated, resulting in an increase in MDA and relative conductivity. Antioxidant enzymes (including SOD, POD, CAT, and APX) and antioxidants (including flavonoids, total phenols, and carotenoids) were decreased. The qPCR results further showed that the expression of the , and , , , , and genes was downregulated, which was consistent with the results of physiological data. Otherwise, the resistance of to high temperature was better than that of , which made it a superior plant in the invasion area. These results further indicated that the gradual warming of global temperature will greatly accelerate the invasion area of .
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http://dx.doi.org/10.3390/ijms22020748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828476PMC
January 2021

-Induced Downregulation of lncRNA Gm28309 Triggers Macrophages Inflammatory Response Through the miR-3068-5p/NF-κB Pathway.

Front Immunol 2020 22;11:581517. Epub 2020 Dec 22.

State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China.

Objectives: The underlying mechanism of the inflammatory response against Brucellosis caused by remains poorly understood. This study aimed to determine the role of long non-coding RNAs (lncRNAs) in regulating of inflammatory and anti- responses.

Materials And Methods: Microarray analysis was performed to detect differentially expressed lncRNAs in THP-1 cells infected with an S2308 strain. The candidate lncRNAs were screened using bioinformatic analysis and siRNAs; bioinformatic prediction and luciferase reporter assay were also conducted, while inflammatory responses was assessed using RT-qPCR, western blot, immunofluorescence, ELISA, HE, and immunohistochemistry.

Results: The lncRNA Gm28309 was identified to be involved in regulating inflammation induced by Gm28309, localized in the cytoplasm, was down-expressed in RAW264.7 cells infected with S2308. Overexpression of Gm28309 or inhibition of miR-3068-5p repressed p65 phosphorylation and reduced NLRP3 inflammasome and IL-1β and IL-18 secretion. Mechanistically, Gm28309 acted as a ceRNA of miR-3068-5p to activate NF-κB pathway by targeting κB-Ras2, an inhibitor of NF-κB signaling. Moreover, the number of intracellular was higher when Gm28309 was overexpressed or when miR-3068-5p or p65 was inhibited. However, these effects were reversed by the miR-3068-5p mimic.

Conclusions: Our study demonstrates, for the first time, that LncRNAs are involved in regulating immune responses during infection, and Gm28309, an lncRNA, plays a crucial role in activating NF-κB/NLRP3 inflammasome signaling pathway.
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http://dx.doi.org/10.3389/fimmu.2020.581517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784117PMC
June 2021

High-Throughput Identification of Antibacterials Against .

Front Microbiol 2020 9;11:591426. Epub 2020 Dec 9.

Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.

Antibiotic resistance is a growing public health concern, though the constant development of new antibiotics. The combination of high-throughput screening and drug repurposing is an effective way to develop new therapeutic uses of drugs. In this study, we screened a drug library consisting of 1,573 drugs already approved by the Food and Drug Administration and 903 drugs from the natural product library, to identify antimicrobials against . A high-throughput screening assay based on microtiter plate was used to screen 39 drugs that inhibit the planktonic or biofilm formation of while most of them are antibiotics. The antimicrobial activities of these drugs were evaluated by phenotypic analysis. Further studies showed the combined therapy of tetracycline antibiotics demeclocycline hydrochloride (DMCT) and the novel antimicrobial peptide SAAP-148 has an effective synergistic antibacterial effect on PAO1 and ATCC27853. Moreover, the time-kill curve assay and murine model of cutaneous abscesses further confirmed the synergistic effect. In addition, the combination of DMCT and SAAP-148 has the potential to combat clinically isolated multidrug-resistant (MDR) strains. Our results clearly indicate that DMCT and SAAP-148 combined therapy could be an effective method to combat MDR -related infections.
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http://dx.doi.org/10.3389/fmicb.2020.591426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755642PMC
December 2020

Application of Near-Infrared Spectroscopy Analysis Technology to Total Nucleosides Quality Control in the Fermented Cordyceps Powder Production Process.

J Anal Methods Chem 2020 28;2020:8850437. Epub 2020 Nov 28.

Key Laboratory of Modern Chinese Medicine Preparation, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.

Product quality control is a prerequisite for ensuring safety, effectiveness, and stability. However, because of the different strain species and fermentation processes, there was a significant difference in quality. As a result, they should be clearly distinguished in clinical use. Among them, the fermentation process is critical to achieving consistent product quality. This study aims to introduce near-infrared spectroscopy analysis technology into the production process of fermented Cordyceps powder, including strain culture, strain passage, strain fermentation, strain filtration, strain drying, strain pulverizing, and strain mixing. First, high performance liquid chromatography (HPLC) was used to measure the total nucleosides content in the production process of 30 batches of fermented Cordyceps powder, including uracil, uridine, adenine, guanosine, adenosine, and the process stability and interbatch consistency were analyzed with traditional Chinese medicine (TCM) fingerprinting, followed by the near-infrared spectroscopy (NIRS) combined with partial least squares regression (PLSR) to establish a quantitative analysis model of total nucleosides for online process monitoring of fermented Cordyceps powder preparation products. The model parameters indicate that the established model with good robustness and high measurement precision. It further clarifies that the model can be used for online process monitoring of fermented Cordyceps powder preparation products.
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http://dx.doi.org/10.1155/2020/8850437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737463PMC
November 2020

Drug repurposing: Antimicrobial and antibiofilm effects of penfluridol against Enterococcus faecalis.

Microbiologyopen 2021 01 20;10(1):e1148. Epub 2020 Dec 20.

Department of Clinical Laboratory, The Third Xiangya Hospital of Central South University, Changsha, China.

The bacterium Enterococcus faecalis has increasingly attracted global attention as an important opportunistic pathogen due to its ability to form biofilms that are known to increase drug resistance. However, there are still no effective antibiofilm drugs in clinical settings. Here, by drug repurposing, we investigated the antibacterial activity of penfluridol (PF), an oral long-acting antipsychotic approved by the FDA, against E. faecalis type strain and its clinical isolates. It was found that PF inhibited the growth of E. faecalis planktonic cells with the MIC and MBC of 7.81 µg/ml and 15.63 ~ 62.50 µg/ml, respectively. Moreover, PF could significantly prevent the biofilm formation of E. faecalis at the concentration of 1 × MIC. Furthermore, PF significantly eradicated 24 h pre-formed biofilms of E. faecalis in a dose-dependent manner, with a concentration range of 1 × MIC to 8 × MIC. Here, through the checkerboard method with other tested conventional antibiotics, we also determined that gentamycin, penicillin G, and amikacin showed partial synergistic antibacterial effects with PF. Also, PF showed almost no hemolysis on human erythrocytes. In a mouse peritonitis model, a single dose of 20 mg/kg of PF treatment could significantly reduce the bacterial colonization in the liver (~5-fold reduction) and spleen (~3-fold reduction). In conclusion, these findings indicated that after structural optimization, PF has the potential as a new antibacterial agent against E. faecalis.
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http://dx.doi.org/10.1002/mbo3.1148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884926PMC
January 2021

Neonatal hyperbilirubinemia management: Clinical assessment of bilirubin production.

Semin Perinatol 2021 Feb 1;45(1):151351. Epub 2020 Dec 1.

Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, CA, USA.

The predominant cause of elevated total/plasma bilirubin (TB) levels is from an increase in bilirubin production primarily because of ongoing hemolysis. If undiagnosed or untreated, the risk for developing extreme neonatal hyperbilirubinemia and possibly bilirubin-induced neurological dysfunction (BIND) is increased. Since carbon monoxide (CO) and bilirubin are produced in equimolar amounts during the heme catabolic process, measurements of end-tidal CO levels, corrected for ambient CO (ETCOc) can be used as a direct indicator of ongoing hemolysis. A newly developed point-of-care ETCOc device has been shown to be a useful for identifying hemolysis-associated hyperbilirubinemia in newborns. This review summarizes the biology of bilirubin production, the clinical utility of a novel device to identify neonates undergoing hemolysis, and a brief introduction on the use of ETCOc measurements in a cohort of neonates in China.
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http://dx.doi.org/10.1016/j.semperi.2020.151351DOI Listing
February 2021

[Analysis of AVPR2 variant in a neonate with congenital nephrogenic diabetes insipidus].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Dec;37(12):1376-1379

Department of Neonatology, Children's Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, China.

Objective: To detect potential variant in a male neonate affected with congenital nephrogenic diabetes insipidus (CNDI).

Methods: Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples from the child and his parents. The whole coding regions of the arginine vasopressin V2 receptor (AVPR2) gene were amplified by PCR and subjected to Sanger sequencing.

Results: The patient presented recurrent fever and polyuria after birth. Multiple blood gas analyses indicated hypernatremia. Ultrasound showed bilateral hydronephrosis and hydroureter. The patient was partially responsive to hydrochlorothiazide. DNA analysis identified a hemizygous frameshift variant c.890-899delACCCGGAGGC in exon 2 of the AVPR2 gene in the proband. His mother was heterozygous for the same variant.

Conclusion: The c.890-899delACCCGGAGGC variant of the AVPR2 gene probably underlies the CNDI in the child. Above discovery has enriched to spectrum of CNDI associated variants.
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http://dx.doi.org/10.3760/cma.j.cn511374-20190808-00403DOI Listing
December 2020
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