Publications by authors named "Meng Yu"

591 Publications

Critical roles of cytokine storm and secondary bacterial infection in acute kidney injury development in COVID-19: A multi-center retrospective cohort study.

J Med Virol 2021 Jul 27. Epub 2021 Jul 27.

Department of Nephrology, the First Hospital Affiliated to Jinan University, Guangzhou, 510630, China.

Acute kidney injury (AKI) may develop in patients with coronavirus disease 2019 (COVID-19) and is associated with in-hospital death.We investigated the incidence of AKI in 223 hospitalized COVID-19 patients and analyzed the influence factors of AKI. The incidence of cytokine storm syndrome and its correlation with other clinicopathologic variables were also investigated. We retrospectively enrolled adult patients with virologically-confirmed COVID-19 who were hospitalized at three hospitals in Wuhan and Guizhou, China between February 13, 2020 and April 8, 2020. We included 124 patients with moderate COVID-19 and 99 with severe COVID-19. AKI was present in 35 (15.7%) patients. The incidence of AKI was 30.3% for severe COVID-19 and 4.0% for moderate COVID-19 (P<0.001). Furthermore, cytokine storm was in 30 (13.5%) patients and only in severe group. Kidney injury at admission (OR 3.132, 95%CI 1.150-8.527; P=0.025), cytokine storm (OR 4.234, 95%CI 1.361-13.171; P=0.013) and acute respiratory distress syndrome (ARDS) (OR 7.684, 95%CI 2.622-22.523; P<0.001) were influence factors of AKI. Seventeen (48.6%) patients who received invasive mechanical ventilation developed AKI, of whom 64.7% (11/17) died. Up to 86.7% AKI patients with cytokine storm may develop secondary bacterial infection. The leukocyte counts were significantly higher in AKI patients with cytokine storm than those without (13.0×10⁹/L, IQR 11.3 vs. 8.3×10⁹/L, IQR 7.5, P=0.005). Approximately 1/6 patients with COVID-19 eventually develop AKI. Kidney injury at admission, cytokine storm and ARDS are influence factors of AKI. Cytokine storm and secondary bacterial infections may be responsible for AKI development in COVID-19 patients. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jmv.27234DOI Listing
July 2021

Identification of prognostic alternative splicing events in sarcoma.

Sci Rep 2021 Jul 22;11(1):14949. Epub 2021 Jul 22.

Department of Emergency Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Sarcoma is a rare malignancy with unfavorable prognoses. Accumulating evidence indicates that aberrant alternative splicing (AS) events are generally involved in cancer pathogenesis. The aim of this study was to identify the prognostic value of AS-related survival genes as potential biomarkers, and highlight the functional roles of AS events in sarcoma. RNA-sequencing and AS-event datasets were downloaded from The Cancer Genome Atlas (TCGA) sarcoma cohort and TCGA SpliceSeq, respectively. Survival-related AS events were further assessed using a univariate analysis. A multivariate Cox regression analysis was also performed to establish a survival-gene signature to predict patient survival, and the area-under-the-curve method was used to evaluate prognostic reliability. KOBAS 3.0 and Cytoscape were used to functionally annotate AS-related genes and to assess their network interactions. We detected 9674 AS events in 40,184 genes from 236 sarcoma samples, and the 15 most significant genes were then used to construct a survival regression model. We further validated the involvement of ten potential survival-related genes (TUBB3, TRIM69, ZNFX1, VAV1, KCNN2, VGLL3, AK7, ARMC4, LRRC1, and CRIP1) in the occurrence and development of sarcoma. Multivariate survival model analyses were also performed, and validated that a model using these ten genes provided good classifications for predicting patient outcomes. The present study has increased our understanding of AS events in sarcoma, and the gene-based model using AS-related events may serve as a potential predictor to determine the survival of sarcoma patients.
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http://dx.doi.org/10.1038/s41598-021-94485-xDOI Listing
July 2021

GGC Repeat Expansion in the Gene Is Associated With a Phenotype of Predominant Motor-Sensory and Autonomic Neuropathy.

Front Genet 2021 7;12:694790. Epub 2021 Jul 7.

Department of Neurology, Peking University First Hospital, Beijing, China.

There is still a considerable proportion of patients with inherited peripheral neuropathy (IPN) whose pathogenic genes are unknown. This study was intended to investigate whether the GGC repeat expansion in the is presented in some patients with IPN. A total of 142 unrelated mainland Chinese patients with highly suspected diagnosis of IPN without any known causative gene were recruited. Repeat-primed polymerase chain reaction (RP-PCR) was performed to screen GGC repeat expansion in , followed by fluorescence amplicon length analysis-PCR (AL-PCR) to determine the GGC repeat size. Detailed clinical data as well as nerve, muscle, and skin biopsy were reviewed and analyzed in the -related IPN patients. In total, five of the 142 patients (3.52%) were found to have pathogenic GGC expansion in , with repeat size ranging from 126 to 206 repeats. All the -related IPN patients presented with adult-onset motor-sensory and autonomic neuropathy that predominantly affected the motor component of peripheral nerves. While tremor and irritating dry cough were noted in four-fifths of the patients, no other signs of the central nervous system were presented. Electrophysiological studies revealed both demyelinating and axonal changes of polyneuropathy that were more severe in lower limbs and asymmetrically in upper limbs. Sural nerve pathology was characterized by multiple fibers with thin myelination, indicating a predominant demyelinating process. Muscle pathology was consistent with neuropathic changes. P62-positive intranuclear inclusions were observed in nerve, skin, and muscle tissues. Our study has demonstrated that GGC expansion in is associated with IPN presenting as predominant motor-sensory and autonomic neuropathy, which expands the phenotype of the -related repeat expansion spectrum. Screening of GGC repeat expansions in the should be considered in patients presenting with peripheral neuropathy with tremor and irritating dry cough.
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http://dx.doi.org/10.3389/fgene.2021.694790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293674PMC
July 2021

5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding.

Mol Psychiatry 2021 Jul 21. Epub 2021 Jul 21.

Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.

Obesity is primarily a consequence of consuming calories beyond energetic requirements, but underpinning drivers have not been fully defined. 5-Hydroxytryptamine (5-HT) neurons in the dorsal Raphe nucleus (5-HT) regulate different types of feeding behavior, such as eating to cope with hunger or for pleasure. Here, we observed that activation of 5-HT to hypothalamic arcuate nucleus (5-HT → ARH) projections inhibits food intake driven by hunger via actions at ARH 5-HT and 5-HT receptors, whereas activation of 5-HT to ventral tegmental area (5-HT → VTA) projections inhibits non-hunger-driven feeding via actions at 5-HT receptors. Further, hunger-driven feeding gradually activates ARH-projecting 5-HT neurons via inhibiting their responsiveness to inhibitory GABAergic inputs; non-hunger-driven feeding activates VTA-projecting 5-HT neurons through reducing a potassium outward current. Thus, our results support a model whereby parallel circuits modulate feeding behavior either in response to hunger or to hunger-independent cues.
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http://dx.doi.org/10.1038/s41380-021-01220-zDOI Listing
July 2021

Myeloperoxidase in the pericardial fluid improves the performance of prediction rules for postoperative atrial fibrillation.

J Thorac Cardiovasc Surg 2021 Jun 22. Epub 2021 Jun 22.

Beijing Chao-yang Hospital affiliated to Capital Medical University, Beijing, P.R. China.

Objectives: After surgery, inflammation is a prominent factor influencing postoperative atrial fibrillation. Myeloperoxidase is a major contributor to inflammatory responses after surgical tissue damage. We evaluated whether myeloperoxidase is associated with postoperative atrial fibrillation clinically and in an animal model.

Methods: This prospective cohort study included patients undergoing isolated coronary artery bypass grafting. Myeloperoxidase concentrations in blood and pericardial fluid were determined at baseline and 6, 12, and 18 hours after coronary artery bypass grafting. Myeloperoxidase activity in blood, pericardial fluid, and atrium were also evaluated in a canine coronary artery bypass grafting model. Electrophysiologic, histologic, and immunohistochemistry analyses were performed to explore underlying mechanisms.

Results: Postoperative atrial fibrillation occurred in 45 of 137 patients (32.8%). Patients with postoperative atrial fibrillation had significantly higher serum and pericardial myeloperoxidase levels. Individual clinical and surgical factors had moderate predictive value (area under the curve, 0.760) for postoperative atrial fibrillation. Discrimination improved remarkably when myeloperoxidase was combined with other parameters (area under the curve, 0.901). Pericardial myeloperoxidase at 6 hours postoperatively was the strongest independent predictor of postoperative atrial fibrillation (odds ratio, 19.215). The rate of postoperative atrial fibrillation increased exponentially across pericardial myeloperoxidase grades. Compared with controls, coronary artery bypass grafting-treated dogs showed higher atrial fibrillation vulnerability and maintenance, shorter atrial effective refractory period, attenuated connexin 43 expression, and increased myocardial and pericardial myeloperoxidase activity. Connexin 43 expression and atrial effective refractory period were strongly negatively correlated with myocardial and pericardial myeloperoxidase activity.

Conclusions: Myeloperoxidase is linked to postoperative atrial fibrillation, and the ability to predict postoperative atrial fibrillation was remarkably improved by adding pericardial myeloperoxidase. Myeloperoxidase-related atrial structural and electrical remodeling is a physiologic substrate for this arrhythmia.
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http://dx.doi.org/10.1016/j.jtcvs.2021.06.027DOI Listing
June 2021

Degradation and Aging of Terrestrial Organic Carbon within Estuaries: Biogeochemical and Environmental Implications.

Environ Sci Technol 2021 Jul 18. Epub 2021 Jul 18.

Frontiers Science Center for Deep Ocean Multispheres and Earth System, and Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, Ocean University of China, Qingdao 266100, China.

Estuaries are action zones for organic carbon (OC) degradation and aging. These processes influence the nature of terrestrial OC (OC) export and the magnitude of OC burial in marginal seas, with important environmental implications such as CO release and hypoxia. In this study, we determined the contents and carbon isotopic compositions (C and C) of bulk OC and fatty acids (FAs) as well as the sedimentological characteristics of suspended particulate matter (SPM) samples collected from two sites over four seasons and of surface sediment samples from three sites in the Pearl River estuary (PRE) to evaluate processes controlling OC degradation and aging along an estuarine gradient. We found that the abundance-weighted average CFA C ages increased by an average of ∼1170 years for SPM and by an average of ∼3440 years in PR/PRE sediments, along the ∼60 km PRE transect. These increases in the FA age coincided with an 86% decrease in the corresponding mineral surface area-normalized FA loading along the sediment transport pathway, implying that selective degradation of labile and younger OC resulted in apparent OC aging. These measurements reveal an important shift in the nature of OC, with implications for biogeochemical cycling within estuaries and for regional environmental changes.
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http://dx.doi.org/10.1021/acs.est.1c02742DOI Listing
July 2021

Global and gene-specific promoter methylation, and micronuclei induction in lead-exposed workers: A cross-sectional study.

Environ Mol Mutagen 2021 Jul 16. Epub 2021 Jul 16.

School of Public Health, and Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China.

Perturbation of epigenetic regulation is a well-established mechanism for cancer but its role for lead (Pb)-associated toxicity has not been adequately investigated. We aimed to investigate whether occupational Pb exposure is associated with micronuclei (MN) frequency and to further explored the mediating roles of epigenetic gene regulation. All the Pb-exposed workers recruited from a Chinese acid battery factory, blood lead levels (BLLs) and MN frequency in lymphocytes were measured. In addition, methylation levels of seven genes (Line-1, RASSF1A, RUNX3, p16, CYP26C1, hMLH1, p15) were examined among 230 workers. Robust Poisson regression model was used to investigate the association between BLLs and MN frequency. Mediation analysis was used to explore the mediating role of specific DNA methylation. Among total 677 participants, 71% were male, median BLLs was 229.1 μg/L (P  = 155.5, P  = 319.3; ranged from 8.9 to 647.7 μg/L), mean MN frequency was 2.5‰ (SD = 1.8‰; ranged from 0 to 9‰). Results from base model, adjusted for age, sex, and body mass index, showed that MN frequency would increase 1.38 (95%confidential interval: 1.34, 1.43) per 100 μg/L increment in BLLs. Using categorized exposure variable analyses, a BLLs dose-response increase in MN frequency was observed: 2.74 (2.13, 3.51), 3.43 (2.73, 4.32), 4.41 (3.89, 5.01) to 6.86 (6.02, 7.81). Mediation analysis indicated that Line-1 methylation significantly mediated 3.6% of the association of BLLs with MN frequency. Occupational Pb exposure induces MN frequency in a dose-response relationship. Part of this association was mediated by Line-1 promotor methylation.
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http://dx.doi.org/10.1002/em.22451DOI Listing
July 2021

Graphene-based nanomaterials for breast cancer treatment: promising therapeutic strategies.

J Nanobiotechnology 2021 Jul 15;19(1):211. Epub 2021 Jul 15.

Breast Center, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Breast cancer is the most common malignancy in women, and its incidence increases annually. Traditional therapies have several side effects, leading to the urgent need to explore new smart drug-delivery systems and find new therapeutic strategies. Graphene-based nanomaterials (GBNs) are potential drug carriers due to their target selectivity, easy functionalization, chemosensitization and high drug-loading capacity. Previous studies have revealed that GBNs play an important role in fighting breast cancer. Here, we have summarized the superior properties of GBNs and modifications to shape GBNs for improved function. Then, we focus on the applications of GBNs in breast cancer treatment, including drug delivery, gene therapy, phototherapy, and magnetothermal therapy (MTT), and as a platform to combine multiple therapies. Their advantages in enhancing therapeutic effects, reducing the toxicity of chemotherapeutic drugs, overcoming multidrug resistance (MDR) and inhibiting tumor metastasis are highlighted. This review aims to help evaluate GBNs as therapeutic strategies and provide additional novel ideas for their application in breast cancer therapy.
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http://dx.doi.org/10.1186/s12951-021-00902-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281664PMC
July 2021

-related autosomal recessive lower motor neuron disease with dysmyelination in peripheral nerves.

Clin Neuropathol 2021 Jul 8. Epub 2021 Jul 8.

Objective: Pleckstrin homology domain-containing family G member 5 () is a nuclear factor-κ-B-activator gene that predominantly expresses in the neurons and Schwann cells of the peripheral nervous system. Variations in the have shown an intermediate form of autosomal recessive Charcot-Marie-Tooth disease and lower motor neuron disease in childhood.

Materials And Methods: This study investigated clinically, electrophysiologically, genetically, and pathologically a young girl with lower motor neuron disease who had weakness and wasting of all limbs starting in early childhood.

Results: Next-generation sequencing found a novel compound heterozygous missense variation c.2038-1G>A and c.1219G>T of gene. Electromyography revealed a neurogenic pattern, and nerve conduction study indicated subclinical sensory neuropathy. Sural biopsy showed hypomyelination, hypermyelination, and infolding myelin membranes coiled into the myelinated axon.

Conclusion: This study identifies, pathologically, novel compound heterozygous mutations and phenotype in -related lower motor neuron disease and dysmyelination in a patient with mutation.
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http://dx.doi.org/10.5414/NP301377DOI Listing
July 2021

Corrigendum: Contrast-Enhanced CT-Based Radiomics Analysis in Predicting Lymphovascular Invasion in Esophageal Squamous Cell Carcinoma.

Front Oncol 2021 17;11:712493. Epub 2021 Jun 17.

Department of Computed Tomography and Magnetic Resonance, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

[This corrects the article DOI: 10.3389/fonc.2021.644165.].
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http://dx.doi.org/10.3389/fonc.2021.712493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248676PMC
June 2021

Salvia miltiorrhiza and Pueraria lobata, two eminent herbs in Xin-Ke-Shu, ameliorate myocardial ischemia partially by modulating the accumulation of free fatty acids in rats.

Phytomedicine 2021 Jun 6;89:153620. Epub 2021 Jun 6.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China. Electronic address:

Background: Xin-Ke-Shu (XKS), a commonly used traditional Chinese medicine, has been clinically proven to be effective for treatment of acute myocardial ischemia (AMI). Numerous studies underscore the important role of fatty acid metabolism in the pathogenesis of AMI.

Purpose: This study examined the relationship between free fatty acids (FFAs) and AMI and the contributions of individual herbs found in XKS to provide a basis for the study of the compatible principle of XKS.

Methods: UFLC-MS/MS-based targeted metabolomics was performed to analyze the levels of 15 FFAs in the plasma and myocardium of isoproterenol (ISO)-induced AMI rats treated with XKS and the subtracted prescriptions of XKS. Electrocardiogram data, H&E staining, biochemical analysis and western blotting were assayed to illustrate the cardioprotection of XKS and its subtracted prescription in AMI. Correlation analysis was used to reveal the relationship between the levels of FFAs and overexpressed proteins/biochemical enzymes.

Results: We found aberrant fatty acid metabolism in AMI rats. In both plasma and myocardium, the concentrations of most of quantified FFAs were significantly altered, whereas the concentrations of stearic acid and behenic acid were similar between the control and AMI groups. Correlation analysis revealed that palmitic acid, oleic acid, linoleic acid and arachidonic acid were potentially the most relevant FFAs to inflammatory and apoptotic proteins and CK-MB. Moreover, XKS effectively alleviated pathological alterations, FFA metabolism abnormity, inflammation and apoptosis found in the myocardium of AMI rats. Notably, the removal of Salvia miltiorrhiza and Pueraria lobata from XKS resulted in markedly regulation loss of cardioprotection during AMI, especially mediation loss of FFA metabolism. The other three herbs of XKS also played a role in improving AMI.

Conclusion: Fatty acid metabolism aberrance occurred during AMI. S. miltiorrhiza and P. lobata play vital roles in the anti-inflammatory and anti-apoptotic action partially by regulating FFA levels. Our findings revealed potential novel clinical FFAs for predicting AMI and extended the insights into the compatible principle of XKS in which S. miltiorrhiza and P. lobata can potently modulate FFA metabolism.
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http://dx.doi.org/10.1016/j.phymed.2021.153620DOI Listing
June 2021

Chronic inflammatory demyelinating polyneuropathy with hypoglossal nerve involvement and inverted Beevor's sign: case report.

BMC Neurol 2021 Jun 26;21(1):244. Epub 2021 Jun 26.

Neurology Department, Peking University First Hospital, No.8 Xishiku Street, Beijing, 100034, China.

Background: Cranial nerve involvement is not commonly encountered in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP); this is especially true for involvement of the hypoglossal nerve. Neither Beevor's sign nor its inverted form has previously been described in CIDP.

Case Presentation: A 28-year-old man presented with distal-predominant limb weakness and numbness at the age of 18. A diagnosis of CIDP was made, which was confirmed by electrodiagnostic evidence of demyelination. He responded well to intravenous immunoglobulin and glucocorticoid treatment and achieved remission for 5 years. However, the same symptoms relapsed at the age of 28 and lasted for 10 months. On examination, in addition to limb sensory impairment and muscle weakness, mild bilateral facial paresis, tongue atrophy and fasciculations, and inverted Beevor's sign were also observed. A brief literature review of cranial nerve involvements in CIDP and Beevor's sign or its inverted form were also performed.

Conclusions: Cranial nerves may be affected in patients with CIDP. Facial palsy is most frequently present, while hypoglossal nerve involvement is rare. Inverted Beevor's sign can appear in CIDP patients.
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http://dx.doi.org/10.1186/s12883-021-02287-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235827PMC
June 2021

Diagnostic Value of Preoperative CA125, LDH and HE4 for Leiomyosarcoma of the Female Reproductive System.

Cancer Manag Res 2021 14;13:4657-4664. Epub 2021 Jun 14.

Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.

Purpose: Leiomyosarcoma (LMS) is a rare and extremely aggressive malignancy that is derived from or shows evidence of differentiation toward smooth muscle. If LMS occurs in the female reproductive system, preoperative diagnosis can be difficult, as LMS is easily mistaken for a uterine leiomyoma, especially a degenerated uterine fibroid (DUF). Thus, we assessed the diagnostic value of the preoperative serum concentrations of cancer antigen 125 (CA125), lactate dehydrogenase (LDH) and human epididymis protein 4 (HE4) for differentiating LMS from DUF.

Patients And Methods: We enrolled patients with LMS or DUF who were receiving treatment in The First Affiliated Hospital of Chongqing Medical University between 2009 and 2020. If the preoperative serum concentrations of CA125, LDH and HE4 of our study participants had been tested, these data were analyzed. The preoperative serum concentrations of CA125, LDH and HE4 in participants with LMS (n = 37) were compared with those of participants with pathologically diagnosed DUF (n = 102), who served as the control group.

Results: The preoperative serum concentrations of CA125, LDH and HE4 of participants with LMS of the female reproductive system were significantly higher than those of participants with DUF ( = 0.009, < 0.001, = 0.001, respectively). The cut-off preoperative serum concentrations of CA125, LDH and HE4 were 30.85 U/mL, 186.50 U/L and 50.50 pmol/L, respectively. When these three parameters were used for an analysis of their combined diagnostic utility, the area under the curve (AUC) was 0.892, the sensitivity was 68.4% and the specificity was 95.1% ( < 0.001).

Conclusion: A combined analysis of the preoperative serum concentrations of CA125, LDH and HE4 could be a promising method for diagnostically differentiating LMS of the female reproductive system from DUF.
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http://dx.doi.org/10.2147/CMAR.S302223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213948PMC
June 2021

The Hierarchical Structure and Predictive Validity of the Personality Inventory for in Chinese Nonclinical Adolescents.

Assessment 2021 Jun 17:10731911211022835. Epub 2021 Jun 17.

Beijing Normal University, Beijing, China.

To evaluate the factor structure, reliability, and validity of the Personality Inventory for (PID-5) in Chinese nonclinical adolescents, a total of 1,442 Chinese middle school youths ( = 14.85, girls = 52.4%) were recruited in the present study. All the participants completed the full-length 220-item PID-5. Some participants ( = 1,003) were administered adolescents' social adjustment as a criterion measure at the same time and 236 participants took part in longitudinal assessment of the PID-5 and adolescents' social adjustment 6 months later. First, exploratory structural equation modeling analyses supported a six-factor structure of the PID-5 in our present sample. Second, Negative Affectivity, Detachment, Antagonistic, and Disinhibition domains had positive correlations with negative social adjustment, and negative correlations with positive social adjustment concurrently and longitudinally, with the exception of Constraint and Psychoticism. Third, Cronbach's alpha for the PID-5 traits ranged from .57 to .91 in the full sample. The 6-month test-retest reliability by indexes of interclass correlation coefficient showed poor to good stability. As a whole, our findings provided preliminary evidence of the PID-5 as a reliable and valid measure of adolescents' maladaptive personality traits in mainland China.
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http://dx.doi.org/10.1177/10731911211022835DOI Listing
June 2021

Characterization of a salt-resistant fibrinolytic protease of Bacillus licheniformis HJ4 isolated from Hwangseokae jeotgal, a traditional Korean fermented seafood.

Folia Microbiol (Praha) 2021 Jun 14. Epub 2021 Jun 14.

Division of Applied Life Science (BK21 Four), Graduate School, Gyeongsang National University, Jinju, 52828, Korea.

Bacillus licheniformis HJ4 showing strong fibrinolytic activity was isolated from Hwangseokae jeotgal. aprEHJ4, a major fibrinolytic gene, was cloned by PCR, and an ORF consisting of 379 amino acids was located. The mature enzyme was expected to be 27 kDa in size after processing, but a 24-kDa protein was observed by SDS-PAGE and fibrin zymography, indicating additional processing. RT-qPCR showed that expression level of aprEHJ4 in culture with 0% salt (control) was the highest followed by culture with 8% salt (89.7% of control) and 5% salt (74.2%) at 84 h. The expression level in culture with 15% salt was 46.9%. The results matched with the fibrinolytic activity measurements of cultures and indicated that AprEHJ4 maintained significant activity in the presence of salt up to 15% (w/v). AprEHJ4 was overproduced in Escherichia coli, and mature 27 kDa protein was purified after in vitro renaturation. The optimum pH and temperature of AprEHJ4 were pH 8 and 40 ℃, respectively.
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http://dx.doi.org/10.1007/s12223-021-00878-wDOI Listing
June 2021

Calycosin-loaded nanoliposomes as potential nanoplatforms for treatment of diabetic nephropathy through regulation of mitochondrial respiratory function.

J Nanobiotechnology 2021 Jun 13;19(1):178. Epub 2021 Jun 13.

Department of Nephrology, The First Hospital Affiliated To Jinan University, NO.613, Huangpu Avenue West, Guangzhou, 510150, China.

Backgrounds: One of the most common complications in diabetic nephropathy is generation of high levels of ROS which can be regulated by herbal antioxidants. However, polyphenols like calycosin, the bioactive compound of Radix astragali suffer from low solubility and poor bioavailability.

Methods: Therefore, in the present study, calycosin-loaded nanoliposomes were fabricated and characterized by TEM, DLS and FTIR techniques. Afterwards, the drug loading (DL) and entrapment efficiency (EE), drug release, solubility, stability, and pharmacodynamic assays were performed. Finally, the antinephropathic effects of calycosin-loaded-nanoliposomes on mitochondria of kidney cells were explored by MTT, ROS, MDA, mitochondrial respiratory function assays.

Results: The result showed that the size, hydrodynamic radius, zeta potential, EE, and DL were, 80 nm, 133.99 ± 21.44 nm, - 20.53 ± 3.57, 88.37 ± 2.28%, and 7.48 ± 1.19%, respectively. The outcomes of in vitro release assay showed that calycosin-loaded nanoliposomes were significantly slow-release in dialysis media with pH 1.2, pH 6.9 and pH 7.4, at about 30 min, the dissolution of calycosin from nanoliposome became almost complete, and after 2 months, the calycosin-loaded nanoliposomes were still stable. Pharmacokinetic assay revealed that the AUC of calycosin in calycosin-loaded nanoliposome group was 927.39 ± 124.91 μg/L*h, which was 2.26 times than that of the free calycosin group (**P < 0.01). Additionally, the MRT and t of calycosin in the calycosin-loaded nanoliposome group were prolonged by 1.54 times and 1.33 times than that of free calycosin group, respectively (*P < 0.05). Finally, it was shown that calycosin-loaded nanoliposomes regulated the viability, ROS production, lipid peroxidation and function of mitochondria in kidney cells of diabetic rats as a model of diabetic nephropathy.

Conclusion: In conclusion it may be suggested that new therapies based on nano-formulated calycosin can restore mitochondrial function which can improve diabetic nephropathy.
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http://dx.doi.org/10.1186/s12951-021-00917-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201677PMC
June 2021

The Micro-RNA Cargo of Extracellular Vesicles Released by Human Adipose Tissue-Derived Mesenchymal Stem Cells Is Modified by Obesity.

Front Cell Dev Biol 2021 20;9:660851. Epub 2021 May 20.

Department of Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United States.

Obesity is a chronic disease that interferes with normal repair processes, including adipose mesenchymal stem/stromal cells (ASCs) function. ASCs produce extracellular vesicles (EVs) that activate a repair program in recipient cells partly via their micro-RNA (miRNA) cargo. We hypothesized that obesity alters the miRNA expression profile of human ASC-derived EVs, limiting their capacity to repair injured cells. Human ASCs were harvested from obese and age- and gender-matched non-obese (lean) subjects during bariatric or cosmetic surgeries, respectively ( = 5 each), and their EVs isolated. Following high-throughput sequencing analysis, differentially expressed miRNAs were identified and their gene targets classified based on cellular component, molecular function, and biological process. The capacity of human lean- and obese-EVs to modulate inflammation, apoptosis, as well as mitogen-activated protein kinase (MAPK) and Wnt signaling in injured human proximal tubular epithelial (HK2) cells was evaluated . The number of EVs released from lean- and obese-ASCs was similar, but obese-EVs were smaller compared to lean-EVs. Differential expression analysis revealed 8 miRNAs upregulated (fold change > 1.4, < 0.05) and 75 downregulated (fold change < 0.7, < 0.05) in obese-EVs vs. lean-EVs. miRNAs upregulated in obese-EVs participate in regulation of NFk-B and MAPK signaling, cytoskeleton organization, and apoptosis, whereas those downregulated in obese-EVs are implicated in cell cycle, angiogenesis, and Wnt and MAPK signaling. Treatment of injured HK2 cells with obese-EVs failed to decrease inflammation, and they decreased apoptosis and MAPK signaling significantly less effectively than their lean counterparts. Obesity alters the size and miRNA cargo of human ASC-derived EVs, as well as their ability to modulate important injury pathways in recipient cells. These observations may guide development of novel strategies to improve healing and repair in obese individuals.
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http://dx.doi.org/10.3389/fcell.2021.660851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173369PMC
May 2021

Antidepressant-like effect and phytochemical profile of supercritical CO₂ extract from .

Pharmazie 2021 Jun;76(6):249-255

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Bei Jing, China;, Email:

is a condiment, adding much flavor in Chinese food. Also it can be used to treat depression as a Traditional Chinese Medicine (TCM). The study here aimed to evaluate the antidepressant effect between the supercritical CO₂ extract () from and the essential oil extracted by steam distillation (). And chemical compositions of were qualitatively analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and gas chromatography-mass spectrometry (GC-MS). Compared with , showed a stronger antidepressant-like effect in FST and TST mice. And it also decreased the content of monoamine oxidase (MAO) in the cerebral cortex of stressed mice. A total of 60 compounds were identified in . Among them, 28 compounds were characterized in UPLC-Q-TOF/MS analysis and all are polymethoxyflavones (PMFs). Three main compounds, 3,5,6,7,8,3',4'-heptamethoxyflavone, nobiletin and tangeretin, together account for 66.09% of the total relative peak area. 33 terpenes were identified by GC-MS analysis, such as D-limonene (12.34%), -elemene (8.86%), germacrene D (5.59%) and (Z, E)--farnesene (5.44%). Polymethoflavones and terpenes are the main constituents of responsible for its antidepressant-like effect. The study could stimulate further investigations into the antidepressant effects and mechanism of .
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http://dx.doi.org/10.1691/ph.2021.1408DOI Listing
June 2021

The effect of the synchronized multi-dimensional policies on imported COVID-19 curtailment in China.

PLoS One 2021 1;16(6):e0252224. Epub 2021 Jun 1.

School of Economics and Management, Shanghai Maritime University, Shanghai, China.

As countries are lifting restrictions and resuming international travels, the rising risk of COVID-19 importation remains concerning, given that the SARS-CoV-2 virus could be transmitted unintentionally through the global transportation network. To explore and assess the effective strategies for curtailing the epidemic risk from international importation nationwide, we evaluated "the joint prevention and control" mechanism, which made up of 19 containment policies, on how it impacted the change of medical observation and detection time from border arrival to laboratory confirmation of COVID-19 in its burst in China. Based on 1,314 epidemiological-survey cases from February 29 to May 25, 2020, we found that the synchronized approach of implementing multi-dimensional interventional policies, such as a centralized quarantine and nucleic acid testing (NAT), flight service adjustment and border closure, effectively facilitate early identification of infected case. Specifically, the implementation of the international flight service reduction was found to be associated with a reduction of the mean intervals of diagnosis from arrival to lab-confirmation by 0.44 days maximally, and the border closure was associated with a reduction of the diagnosis interval of imported cases by 0.69 days, from arrival to laboratory confirmation. The study suggests that a timely and synchronized implementation of multi-dimensional policies is compelling in preventing domestic spreading from importation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252224PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168853PMC
June 2021

Aerophilic Co-Embedded N-Doped Carbon Nanotube Arrays as Highly Efficient Cathodes for Aluminum-Air Batteries.

ACS Appl Mater Interfaces 2021 Jun 1;13(23):26853-26860. Epub 2021 Jun 1.

State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.

Recently, aluminum-air batteries have attracted great interest owing to their high output energy density, low cost, and feasibility to store and transport Al metal. However, the commercial application is still hindered by the lack of a high-performance air cathode, where the oxygen reduction reaction (ORR) happens, requiring fast charge transfer and mass transport at the catalyst-electrolyte-air interface. Herein, we report an aerophilic air cathode featuring both high intrinsic catalytic activity and large three-phase interface to facilitate air transport, which is prepared by growing cobalt-embedded and nitrogen-doped carbon nanotube (CoNCNT) arrays on carbon fiber paper and then modifying surface wettability with polytetrafluoroethylene solution. The optimized air electrode during the ORR shows a high onset potential of 0.95 V and fast current increase of 342.96 mA cm V, which is comparable to the commercial 20 wt % Pt/C, and has even better stability under the same conditions. Moreover, the aluminum-air battery with the aerophilic air electrode is superior to the battery with a commercial Pt/C electrode or aerophobic electrode in terms of maximum power density and long discharging durability. Bubble behavior measurement shows that aerobic wettability plays an important role in gas transport, thus controlling ORR efficiency of the air electrode. The concept of the gas-wettable electrode proves to be effective in the enhancement of oxygen reduction kinetics and would be also adapted in other gas-involved electrodes for energy-related applications.
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http://dx.doi.org/10.1021/acsami.1c00837DOI Listing
June 2021

Contrast-Enhanced CT-Based Radiomics Analysis in Predicting Lymphovascular Invasion in Esophageal Squamous Cell Carcinoma.

Front Oncol 2021 14;11:644165. Epub 2021 May 14.

Department of Computed Tomography and Magnetic Resonance, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Objectives: To develop a radiomics model based on contrast-enhanced CT (CECT) to predict the lymphovascular invasion (LVI) in esophageal squamous cell carcinoma (ESCC) and provide decision-making support for clinicians.

Patients And Methods: This retrospective study enrolled 334 patients with surgically resected and pathologically confirmed ESCC, including 96 patients with LVI and 238 patients without LVI. All enrolled patients were randomly divided into a training cohort and a testing cohort at a ratio of 7:3, with the training cohort containing 234 patients (68 patients with LVI and 166 without LVI) and the testing cohort containing 100 patients (28 patients with LVI and 72 without LVI). All patients underwent preoperative CECT scans within 2 weeks before operation. Quantitative radiomics features were extracted from CECT images, and the least absolute shrinkage and selection operator (LASSO) method was applied to select radiomics features. Logistic regression (Logistic), support vector machine (SVM), and decision tree (Tree) methods were separately used to establish radiomics models to predict the LVI status in ESCC, and the best model was selected to calculate Radscore, which combined with two clinical CT predictors to build a combined model. The clinical model was also developed by using logistic regression. The receiver characteristic curve (ROC) and decision curve (DCA) analysis were used to evaluate the model performance in predicting the LVI status in ESCC.

Results: In the radiomics model, Sphericity and gray-level non-uniformity (GLNU) were the most significant radiomics features for predicting LVI. In the clinical model, the maximum tumor thickness based on CECT (cThick) in patients with LVI was significantly greater than that in patients without LVI (P<0.001). Patients with LVI had higher clinical N stage based on CECT (cN stage) than patients without LVI (<0.001). The ROC analysis showed that both the radiomics model (AUC values were 0.847 and 0.826 in the training and testing cohort, respectively) and the combined model (0.876 and 0.867, respectively) performed better than the clinical model (0.775 and 0.798, respectively), with the combined model exhibiting the best performance.

Conclusions: The combined model incorporating radiomics features and clinical CT predictors may potentially predict the LVI status in ESCC and provide support for clinical treatment decisions.
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http://dx.doi.org/10.3389/fonc.2021.644165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162215PMC
May 2021

One-Cell Metabolic Phenotyping and Sequencing of Soil Microbiome by Raman-Activated Gravity-Driven Encapsulation (RAGE).

mSystems 2021 Jun 27;6(3):e0018121. Epub 2021 May 27.

Single-Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Institute of Energy Research, Qingdao Institute of BioEnergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China.

Soil harbors arguably the most metabolically and genetically heterogeneous microbiomes on Earth, yet establishing the link between metabolic functions and genome at the precisely one-cell level has been difficult. Here, for mock microbial communities and then for soil microbiota, we established a Raman-activated gravity-driven single-cell encapsulation and sequencing (RAGE-Seq) platform, which identifies, sorts, and sequences precisely one bacterial cell via its anabolic (incorporating D from heavy water) and physiological (carotenoid-containing) functions. We showed that (i) metabolically active cells from numerically rare soil taxa, such as spp., spp., spp., spp., and Pseudomonas spp., can be readily identified and sorted based on DO uptake, and their one-cell genome coverage can reach ∼93% to allow high-quality genome-wide metabolic reconstruction; (ii) similarly, carotenoid-containing cells such as spp., spp., spp., Pseudomonas spp., and spp. were identified and one-cell genomes were generated for tracing the carotenoid-synthetic pathways; and (iii) carotenoid-producing cells can be either metabolically active or inert, suggesting culture-based approaches can miss many such cells. As a Raman-activated cell sorter (RACS) family member that can establish a metabolism-genome link at exactly one-cell resolution from soil, RAGE-Seq can help to precisely pinpoint "who is doing what" in complex ecosystems. Soil is home to an enormous and complex microbiome that features arguably the highest genomic diversity and metabolic heterogeneity of cells on Earth. Their metabolic activities drive many natural processes of pivotal ecological significance or underlie industrial production of numerous valuable bioactivities. However, pinpointing "who is doing what" in a soil microbiome, which consists of mainly yet-to-be-cultured species, has remained a major challenge. Here, for soil microbiota, we established a Raman-activated gravity-driven single-cell encapsulation and sequencing (RAGE-Seq) method, which identifies, sorts, and sequences at the resolution of precisely one microbial cell via its catabolic and anabolic functions. As a Raman-activated cell sorter (RACS) family member that can establish a metabolism-genome link at one-cell resolution from soil, RAGE-Seq can help to precisely pinpoint "who is doing what" in complex ecosystems.
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http://dx.doi.org/10.1128/mSystems.00181-21DOI Listing
June 2021

Barbadin Potentiates Long-Term Effects of Lorcaserin on POMC Neurons and Weight Loss.

J Neurosci 2021 Jun 24;41(26):5734-5746. Epub 2021 May 24.

Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030

Obesity is a serious global health problem because of its increasing prevalence and comorbidities, but its treatments are limited. The serotonin 2C receptor (5-HTR), a G-protein-coupled receptor, activates proopiomelanocortin (POMC) neurons in the arcuate nucleus of hypothalamus (ARH) to reduce appetite and weight gain. However, several 5-HT analogs targeting this receptor, e.g., lorcaserin (Lor), suffer from diminished efficacy to reduce weight after prolonged administration. Here, we show that barbadin (Bar), a novel β-arrestin/β2-adaptin inhibitor, can prevent 5-HTR internalization in cells and potentiate long-term effects of Lor to reduce appetite and body weight in male mice. Mechanistically, we demonstrate that Bar co-treatment can effectively maintain the sensitivity of the 5-HTR in POMC neurons, despite prolonged Lor exposure, thereby allowing these neurons to be activated through opening the transient receptor potential cation (TRPC) channels. Thus, our results prove the concept that inhibition of 5-HTR desensitization can be a valid strategy to improve the long-term weight loss effects of Lor or other 5-HTR agonists, and also provide an intellectual framework to develop effective long-term management of weight by targeting 5-HTR desensitization. By demonstrating that the combination of barbadin (Bar) with a G-protein-coupled receptor (GPCR) agonist can provide prolonged weight-lowering benefits in a preclinical setting, our work should call for additional efforts to validate Bar as a safe and effective medicine or to use Bar as a lead compound to develop more suitable compounds for obesity treatment. These results prove the concept that inhibition of serotonin 2C receptor (5-HTR) desensitization can be a valid strategy to improve the long-term weight loss effects of lorcaserin (Lor) or other 5-HTR agonists. Since GPCRs represent a major category as therapeutic targets for various human diseases and desensitization of GPCRs is a common issue, our work may provide a conceptual framework to enhance effects of a broad range of GPCR medicines.
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http://dx.doi.org/10.1523/JNEUROSCI.3210-20.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244968PMC
June 2021

Prenatal exposure to organophosphate esters and neonatal thyroid-stimulating hormone levels: A birth cohort study in Wuhan, China.

Environ Int 2021 May 18;156:106640. Epub 2021 May 18.

State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, Hubei 430030, China. Electronic address:

Background: Increasing animal studies have indicated that organophosphate esters (OPEs) have endocrine-disruptive potential. However, human epidemiological evidence is limited, especially in susceptible populations, such as pregnant women and neonates. The purpose of this present study was to examine the trimester-specific relationships of prenatal exposure to OPEs with neonatal thyroid-stimulating hormone (TSH).

Method: A total of 102 mother-newborn pairs were recruited from a birth cohort study between April 2015 and September 2016 in Wuhan, China. Eight OPE metabolites were detectable in urine samples from pregnant women across the different three trimesters. Neonatal TSH levels were measured using time-resolved immunofluorescence assay. The associations between maternal urinary OPE metabolites and neonatal TSH and the critical exposure windows of fetal vulnerability were estimated using multiple informant models.

Results: Seven OPE metabolites with detection frequency > 50% (52.9%-98.0%) were detected in repeated urine samples from different three trimesters, and the urinary OPE metabolites across pregnancy was of high variability (ICCs: 0.09-0.26). After adjusted for confounders (e.g., maternal age, prepregnancy BMI, passive smoking during pregnancy), some suggestive associations were observed between maternal urinary OPE metabolites and neonatal TSH in different trimesters. A doubling of second trimester di-o-cresyl phosphate & di-p-cresyl phosphate (DoCP & DpCP) was associated with a 7.82% increase in neonatal TSH level (95% CI: -0.70%, 17.06%, p-value = 0.07), a doubling of third trimester diphenyl phosphate (DPHP) was associated with a 4.71% decrease in neonatal TSH level (95% CI: -9.80%, 0.67%, p-value = 0.09), and a doubling of third trimester bis(2-butoxyethyl) phosphate (BBOEP) was associated with a 6.38% increase in neonatal TSH level (95% CI: -0.12%, 13.31%, p = 0.05). However, such associations did not differ materially across trimesters. When performing stratified analysis by infant sex, the associations were statistically significant and were sex-dependent.In females, maternal urinary DoCP & DpCP concentrations in each trimester were associated with increased neonatal TSH levels, and urinary DPHP concentration in the third trimester was associated with decreased neonatal TSH level. In males, maternal urinary BBOEP concentration in the first trimester was positively related to neonatal TSH level.

Conclusion: This prospective study demonstrated that prenatal exposure to OPEs can lead to a sex-dependent change in neonatal TSH levels. Although the sex-selective effect was differed among various urinary OPE metabolites, more evidence was supported that OPE exposure was related to increased TSH levels for both males and females.
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http://dx.doi.org/10.1016/j.envint.2021.106640DOI Listing
May 2021

Highly Dispersive Cerium Atoms on Carbon Nanowires as Oxygen Reduction Reaction Electrocatalysts for Zn-Air Batteries.

Nano Lett 2021 May 17;21(10):4508-4515. Epub 2021 May 17.

Fok Ying Tung Research Institute, Hong Kong University of Science and Technology, Guangzhou 511458, China.

Highly efficient noble-metal-free electrocatalysts for oxygen reduction reaction (ORR) are essential to reduce the costs of fuel cells and metal-air batteries. Herein, a single-atom Ce-N-C catalyst, constructed of atomically dispersed Ce anchored on N-doped porous carbon nanowires, is proposed to boost the ORR. This catalyst has a high Ce content of 8.55 wt % and a high activity with ORR half-wave potentials of 0.88 V in alkaline media and 0.75 V in acidic electrolytes, which are comparable to widely studied Fe-N-C catalysts. A Zn-air battery based on this material shows excellent performance and durability. Density functional theory calculations reveal that atomically dispersed Ce with adsorbed hydroxyl species (OH) can significantly reduce the energy barrier of the rate-determining step resulting in an improved ORR activity.
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http://dx.doi.org/10.1021/acs.nanolett.1c01493DOI Listing
May 2021

The phosphorylation of phosphoglucosamine mutase GlmM by Ser/Thr kinase STK mediates cell wall synthesis and virulence in Streptococcus suis serotype 2.

Vet Microbiol 2021 Jul 6;258:109102. Epub 2021 May 6.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China. Electronic address:

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes serious economic losses in the pig industry. Phosphorylation is an important mechanism of protein modification. Recent studies have reported that the serine/threonine kinase (STK) gene contributes to the growth and virulence of SS2. However, the mechanism underlying the regulatory functions of STK in SS2 has not been thoroughly elucidated to date. In this study, phosphoproteomic analysis was performed to determine substrates of the STK protein. Twenty-two proteins with different cell functions were identified as potential substrates of STK. Phosphoglucosamine mutase (GlmM) was selected for further investigation among them. In vitro phosphorylation assay and immunoprecipitation assay indicated that GlmM was phosphorylated by STK at the Ser-101 site and the phosphorylation level of GlmM can be affected. We observed that compared to the wild-type strain ZY05719, the glmM-deficient strain (ΔglmM) and the glmM S101A point mutation strain (CΔglmM S101A) showed aberrant cell morphology and attenuated virulence, including enlarged cell volume, absent capsule, decreased resistance, lower survival caused by unusual peptidoglycan synthesis, and significantly attenuated pathogenicity in a mouse infection model. Additionally, compared to ZY05719 and CΔglmM, GlmM enzyme acivities and peptidoglycan concentrations of the stk-deficient strain (Δstk), CΔglmM S101A decreased significantly. These experiments revealed that STK phosphorylates GlmM at the Ser-101 site to impact GlmM enzyme activity and control cell wall peptidoglycan synthesis to affect SS2 pathogenicity.
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http://dx.doi.org/10.1016/j.vetmic.2021.109102DOI Listing
July 2021

Photonic Implementation of Quantum Information Masking.

Phys Rev Lett 2021 Apr;126(17):170505

CAS Key Laboratory of Quantum Information, University of Science and Technology of China, Hefei 230026, People's Republic of China.

Masking of quantum information spreads it over nonlocal correlations and hides it from the subsystems. It is known that no operation can simultaneously mask all pure states [Phys. Rev. Lett. 120, 230501 (2018)PRLTAO0031-900710.1103/PhysRevLett.120.230501], so in what sense is quantum information masking useful? Here, we extend the definition of quantum information masking to general mixed states, and show that the resource of maskable quantum states is far more abundant than the no-go theorem seemingly suggests. Geometrically, the simultaneously maskable states lays on hyperdisks in the state hypersphere, and strictly contains the broadcastable states. We devise a photonic quantum information masking machine using time-correlated photons to experimentally investigate the properties of qubit masking, and demonstrate the transfer of quantum information into bipartite correlations and its faithful retrieval. The versatile masking machine has decent extensibility, and may be applicable to quantum secret sharing and fault-tolerant quantum communication. Our results provide some insights on the comprehension and potential application of quantum information masking.
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http://dx.doi.org/10.1103/PhysRevLett.126.170505DOI Listing
April 2021

Metabolic classification of bladder cancer based on multi-omics integrated analysis to predict patient prognosis and treatment response.

J Transl Med 2021 05 13;19(1):205. Epub 2021 May 13.

Department of Urology, The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, China.

Background: Currently, no molecular classification is established for bladder cancer based on metabolic characteristics. Therefore, we conducted a comprehensive analysis of bladder cancer metabolism-related genes using multiple publicly available datasets and aimed to identify subtypes according to distinctive metabolic characteristics.

Methods: RNA-sequencing data of The Cancer Genome Atlas were subjected to non-negative matrix fractionation to classify bladder cancer according to metabolism-related gene expression; Gene Expression Omnibus and ArrayExpress datasets were used as validation cohorts. The sensitivity of metabolic types to predicted immunotherapy and chemotherapy was assessed. Kaplan-Meier curves were plotted to assess patient survival. Differentially expressed genes between subtypes were identified using edgeR. The differences among identified subtypes were compared using the Kruskal-Wallis non-parametric test. To better clarify the subtypes of bladder cancer, their relationship with clinical characteristics was examined using the Fisher's test. We also constructed a risk prediction model using the random survival forest method to analyze right-censored survival data based on key metabolic genes. To identify genes of prognostic significance, univariate Cox regression, lasso analysis, and multivariate regression were performed sequentially.

Results: Three bladder cancer subtypes were identified according to the expression of metabolism-related genes. The M1 subtype was characterized by high metabolic activity, low immunogenicity, and better prognosis. M2 exhibited moderate metabolic activity, high immunogenicity, and the worst prognosis. M3 was associated with low metabolic activity, low immunogenicity, and poor prognosis. M1 showed the best predicted response to immunotherapy, whereas patients with M1 were predicted to be the least sensitive to cisplatin. By contrast, M2 showed the worst predicted response to immunotherapy but was predicted to be more sensitive to cisplatin, doxorubicin, and other first-line anticancer drugs. M3 was the most sensitive to gemcitabine. The risk model based on metabolic genes effectively predicted the prognosis of bladder cancer patients.

Conclusions: Metabolic classification of bladder cancer has potential clinical value and therapeutic feasibility by inhibiting the associated pathways. This classification can provide valuable insights for developing precise bladder cancer treatment.
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http://dx.doi.org/10.1186/s12967-021-02865-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117567PMC
May 2021

Plant multiscale networks: charting plant connectivity by multi-level analysis and imaging techniques.

Sci China Life Sci 2021 Mar 12. Epub 2021 Mar 12.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing, 100083, China.

In multicellular and even single-celled organisms, individual components are interconnected at multiscale levels to produce enormously complex biological networks that help these systems maintain homeostasis for development and environmental adaptation. Systems biology studies initially adopted network analysis to explore how relationships between individual components give rise to complex biological processes. Network analysis has been applied to dissect the complex connectivity of mammalian brains across different scales in time and space in The Human Brain Project. In plant science, network analysis has similarly been applied to study the connectivity of plant components at the molecular, subcellular, cellular, organic, and organism levels. Analysis of these multiscale networks contributes to our understanding of how genotype determines phenotype. In this review, we summarized the theoretical framework of plant multiscale networks and introduced studies investigating plant networks by various experimental and computational modalities. We next discussed the currently available analytic methodologies and multi-level imaging techniques used to map multiscale networks in plants. Finally, we highlighted some of the technical challenges and key questions remaining to be addressed in this emerging field.
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http://dx.doi.org/10.1007/s11427-020-1910-1DOI Listing
March 2021

Control Analysis of Protein-Protein Interaction Network Reveals Potential Regulatory Targets for MYCN.

Front Oncol 2021 21;11:633579. Epub 2021 Apr 21.

Department of Physiology, Shenyang Medical College, Shenyang, China.

Background: MYCN is an oncogenic transcription factor of the MYC family and plays an important role in the formation of tissues and organs during development before birth. Due to the difficulty in drugging MYCN directly, revealing the molecules in MYCN regulatory networks will help to identify effective therapeutic targets.

Methods: We utilized network controllability theory, a recent developed powerful tool, to identify the potential drug target around MYCN based on Protein-Protein interaction network of MYCN. First, we constructed a Protein-Protein interaction network of MYCN based on public databases. Second, network control analysis was applied on network to identify driver genes and indispensable genes of the MYCN regulatory network. Finally, we developed a novel integrated approach to identify potential drug targets for regulating the function of the MYCN regulatory network.

Results: We constructed an MYCN regulatory network that has 79 genes and 129 interactions. Based on network controllability theory, we analyzed driver genes which capable to fully control the network. We found 10 indispensable genes whose alternation will significantly change the regulatory pathways of the MYCN network. We evaluated the stability and correlation analysis of these genes and found EGFR may be the potential drug target which closely associated with MYCN.

Conclusion: Together, our findings indicate that EGFR plays an important role in the regulatory network and pathways of MYCN and therefore may represent an attractive therapeutic target for cancer treatment.
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http://dx.doi.org/10.3389/fonc.2021.633579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096904PMC
April 2021
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