Publications by authors named "Ke Huang"

572 Publications

Ultraprecise Real-Time Monitoring of Single Cells in Tumors in Response to Metal Ion-Mediated RNA Delivery.

ACS Appl Mater Interfaces 2022 Aug 16. Epub 2022 Aug 16.

State Key Laboratory of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, School of Biological Science and Medical Engineering, Southeast University, No. 2 Sipailou, Nanjing 210096, China.

With the deepening of cancer clinical research, miRNAs provide new ideas for molecular diagnosis and treatment of tumors. Improving the molecular delivery efficiency of miRNA is the key to the success of miRNA therapy. We have established self-assembly diagnosis and treatment technologies that can be used to achieve accurate targeting and "cargo" delivery at the cellular level. This technology builds a miRNA (let-7a) delivery system based on metal precursor [Au(III) and Fe(II)]-mediated tumor microenvironmental response to realize the self-assembly of Au&Fe-miRNA complexes for precise real-time imaging of tumor cells and targeted therapy. To accurately measure the changes in reactive oxygen species during complex formation in real time at the single-cell level, we employed small-size nanoscale devices as analytical tools. This study proposes an electrochemical sensor based on carbon fiber electrodes for ultraprecise and multiple monitoring of metal-ion-mediated miRNA delivery systems, precisely realizing targeted tracking of tumors and effective intervention inhibition.
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http://dx.doi.org/10.1021/acsami.2c06306DOI Listing
August 2022

A Modified Hyaluronic Acid-Based Dissolving Microneedle Loaded With Daphnetin Improved the Treatment of Psoriasis.

Front Bioeng Biotechnol 2022 17;10:900274. Epub 2022 Jun 17.

Department of Dermatology and Rheumatology Immunology, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Psoriasis is a common chronic immune-inflammatory disease. Challenges exist in the present treatment of psoriasis, such as difficulties in transdermal drug administration and severe side effects. We hope to achieve a better therapeutic outcome for psoriasis treatment. By using modified soluble microneedles (MNs) loaded with daphnetin, the psoriasis symptoms of mice, the abnormal proliferation of keratinocytes, and the secretion of inflammatory factors were significantly reduced. , daphnetin is proven to inhibit the NF-κB signaling pathway and to inhibit the proliferation of HaCaT cells and the release of inflammatory factors, especially CCL20. This research showed that the modified microneedle loaded with daphnetin optimized transdermal drug delivery and relieved the symptoms of psoriasis more effectively. The novel route of Daph administration provides a future research direction for the treatment of psoriasis.
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http://dx.doi.org/10.3389/fbioe.2022.900274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367187PMC
June 2022

Smartphone readable colorimetry and ICP-MS dual-mode sensing platform for ultrasensitive and label-free detection of Escherichia coli based on filter-assisted separation.

Talanta 2022 Jul 30;251:123760. Epub 2022 Jul 30.

State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China. Electronic address:

The development and application of portable and user-friendly biosensing technology for rapid detection of pathogenic bacteria are essential for human and environmental care. In this work, based on the phenomenon that the filter membrane can selectively separate MnO nanosheets (MnO NSs) and Mn, a novel label-free sensing platform was developed to detect the Escherichia coli (E. coli) using β-galactosidase (β-Gal) as a marker. MnO NSs were utilized as a dual-mode signal molecule of smartphone-based colorimetric analysis and inductively coupled plasma mass spectrometry (ICP-MS). β-Gal can catalyze the 4-Aminophenyl β-D-galactopyranoside (PAPG) to produce p-aminophenol (PAP), which could reduce MnO NSs to Mn. After selective separation of MnO NSs and Mn by the filter, colorimetric detection was achieved with a smartphone by identifying the RGB value of the MnO NSs coated membrane, while the Mn in the filtrate was detected by ICP-MS. Under optimal conditions, the limits of detection (LODs) of E. coli by smartphone-based RGB analysis and ICP-MS were 5.6 × 10 CFU mL and 35 CFU mL, respectively. This method was successfully used for E. coli assay in meat, vegetables, and fruit samples with the advantages of sensitivity, simplicity, and short incubation time (within 1 h).
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http://dx.doi.org/10.1016/j.talanta.2022.123760DOI Listing
July 2022

Constructing a defect-rich hydroxide nanoenzyme sensor based on dielectric barrier discharge microplasma etching for sensitive detection of thiamine hydrochloride and hydrogen peroxide.

J Colloid Interface Sci 2022 Jul 27;628(Pt A):597-606. Epub 2022 Jul 27.

College of Chemistry and Material Science, Sichuan Normal University, Chengdu, Sichuan 610068, PR China. Electronic address:

In this work, a novel approach was designed to fabricate a defect-rich hydroxide nanoenzyme sensor based on transition metal cobalt derived from metal-organic framework (MOF). Facile preparation was realized by room-temperature reaction and chemical etching via dielectric barrier discharge (DBD) microplasma, which possesses great chemical reactivity to obtain defect-rich and ultrathin structures. The prepared cobalt hydroxide (Co(OH)) emerges with superior catalytic activity for thiamine hydrochloride (TCL) and hydrogen peroxide (HO) assay. The linear ranges were 0.0006 mM to 2.75 mM for TCL detection and 0.001 mM to 5.5 mM for HO detection with low limit of detections (LODs) of 14 nM and 93 nM, respectively. Meanwhile, the as-prepared sensor provides excellent long-term durability (>25 days), as well as high sensitivity (12730 μA mMcm and 5199.3 μA mM cm) for TCL and HO assay. TCL in serum samples has been detected with satisfactory results by the proposed material, while the HO in Hela cells was also successfully measured. The developed sensor provides several advantages including simplicity, high sensitivity, and efficient preparation.
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http://dx.doi.org/10.1016/j.jcis.2022.07.151DOI Listing
July 2022

Risk factors for obesity and overweight in Chinese children: a nationwide survey.

Obesity (Silver Spring) 2022 Aug 2. Epub 2022 Aug 2.

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

Objective: This study aimed to analyze a comprehensive set of potential risk factors for obesity and overweight among Chinese children with a full range of ages and with wide geographical coverage.

Methods: In the Prevalence and Risk Factors for Obesity and Diabetes in Youth (PRODY) study (2017-2019), the authors analyzed 193,997 children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that are geographically representative of China. All participants underwent physical examinations, and their caregivers completed questionnaires including dietary, lifestyle, familial, and perinatal information of participants. A multilevel multinomial logistic regression model was used to evaluate the potential risk factors.

Results: Among the actionable risk factors that were measured, higher consumption frequencies of animal offal (odds ratios [OR] for an additional time/day = 0.91, 95% CI: 0.88-0.95, same unit for OR below unless specified otherwise), dairy products (0.91, 95% CI: 0.88-0.94), freshwater products (0.94, 95% CI: 0.91-0.96), staple foods (0.94, 95% CI: 0.92-0.96), and coarse food grain (OR for every day vs. rarely = 0.92, 95% CI: 0.86-0.98) were associated with lower relative risk of obesity. However, higher restaurant-eating frequency (OR for >4 times/month vs. rarely = 1.21, 95% CI: 1.15-1.29) and longer screen-viewing duration (OR for >2 hours vs. <30 minutes = 1.16, 95% CI: 1.10-1.22) were associated with higher relative risk of obesity. Increased exercise frequency was associated with the lowest relative risk of obesity (OR for every day vs. rarely = 0.72, 95% CI: 0.68-0.77).

Conclusions: Changes in lifestyle and diet of Chinese children may help relieve their obesity burden.
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http://dx.doi.org/10.1002/oby.23515DOI Listing
August 2022

The Tropomyosin Family as Novel Biomarkers in Relation to Poor Prognosis in Glioma.

Biology (Basel) 2022 Jul 26;11(8). Epub 2022 Jul 26.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730030, China.

(1) Background: The functions of the tropomyosin (TPM) family in tumors and cancers have been explored; however, striking differences have been observed. This study aims to further our understanding of the effects of TPMs in glioma, and find novel biomarkers for glioma. (2) Methods: RNA-seq data were downloaded from TCGA and GTEx. Survival analyses, Cox regression, nomogram, calibration curves, ROC curves, gene function enrichment analyses, and immune cell infiltration analyses were carried out using R. CCK8 assay, while Brdu assay, colony formation assay, and Transwell assay were used to verify the functions of TPM3 in glioma. (3) Results: TPM1/3/4 were significantly more highly expressed in glioma than that in normal tissues, while higher expression of TPM2/3/4 was correlated with a worse overall survival than lower expression of TPM2/3/4. Furthermore, bioinformatic analyses indicated that TPM3/4 could be promoting factors for poorer survival in glioma, but only TPM3 could serve as an independent prognostic factor. Gene function analyses showed that TPMs may be involved in immune responses. Moreover, further experimental investigations verified that TPM3 overexpression enhanced the proliferation and tumorigenicity of glioma. (4) Conclusions: High expression of TPM3/4 was positively correlated with poorer prognosis in glioma, and TPM3 could serve as a novel independent prognostic factor of glioma.
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http://dx.doi.org/10.3390/biology11081115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332389PMC
July 2022

Preharvest Methyl Jasmonate Treatment Increased Glucosinolate Biosynthesis, Sulforaphane Accumulation, and Antioxidant Activity of Broccoli.

Antioxidants (Basel) 2022 Jun 29;11(7). Epub 2022 Jun 29.

College of Horticulture, Hunan Agricultural University, Changsha 410128, China.

Broccoli is becoming increasingly popular among consumers owing to its nutritional value and rich bioactive compounds, such glucosinolates (GSLs) and hydrolysis products, which are secondary metabolites for plant defense, cancer prevention, and higher antioxidant activity for humans. In this study, 40 μmol/L methyl jasmonate (MeJA) was sprayed onto broccoli from budding until harvest. The harvested broccoli florets, stem, and leaves were used to measure the contents of GSLs, sulforaphane, total phenolics, and flavonoids, as well as myrosinase activity, antioxidant activity, and gene expression involved in GSL biosynthesis. The overall results revealed that GSL biosynthesis and sulforaphane accumulation were most likely induced by exogenous MeJA treatment by upregulating the expression of , , , and genes. Exogenous MeJA treatment more remarkably contributed to the increased GSL biosynthesis in broccoli cultivars with low-level GSL content (Yanxiu) than that with high-level GSLs (Xianglv No.3). Moreover, MeJA treatment had a more remarkable increasing effect in broccoli florets than stem and leaves. Interestingly, total flavonoid content substantially increased in broccoli florets after MeJA treatment, but total phenolics did not. Similarly, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity, trolox-equivalent antioxidant capacity (ABTS), and ferric-reducing antioxidant power (FRAP) were higher in broccoli floret after MeJA treatment. In conclusion, MeJA mediated bioactive compound metabolism, had positive effects on GSL biosynthesis, sulforaphane, and flavonoids accumulation, and showed positive correlation on inducing higher antioxidant activities in broccoli floret. Hence, preharvest supplementation with 40 μM MeJA could be a good way to improve the nutritional value of broccoli florets.
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http://dx.doi.org/10.3390/antiox11071298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312100PMC
June 2022

Tissue engineered bone via templated hBMSCs mineralization and its application for bone repairing.

Biomater Adv 2022 Aug 30;139:212937. Epub 2022 May 30.

College of Chemistry and Materials Science, Jinan University, No. 601, West Huangpu Avenue, Guangzhou, Guangdong 510632, PR China; Engineering Research Center of Artificial Organs and Materials, Jinan University, Guangzhou 510632, PR China. Electronic address:

To develop bone implants, a novel tissue-engineered bone was constructed via templated human bone mesenchymal stem cells (hBMSCs) mineralization. Firstly, an osteoid-like template (Os-template) with aligned collagen fibers was prepared and followed by seeding hBMSCs to mimic the process of bone formation. After being cultured over weeks, the cells produced collagen fibers in an orderly aligned osteomorphic fashion. Further, a novel tissue-engineered bone with mineralized collagen fiber (mOs-ECM) was subsequently achieved after cell mineralization, showing a high degree of osteomimicry in terms of both composition and structure. When applied to the rat cranial bone defect model, the mOs-ECM significantly promoted the new bone formation and fused with the host bone. The study indicated that microscopic cell mineralization could be guided by artificially designed templates and successfully fabricated a macroscopic implant with a pronounced effect on bone repairing.
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http://dx.doi.org/10.1016/j.bioadv.2022.212937DOI Listing
August 2022

Population Pharmacokinetics and Initial Dosage Optimization of Tacrolimus in Pediatric Hematopoietic Stem Cell Transplant Patients.

Front Pharmacol 2022 6;13:891648. Epub 2022 Jul 6.

Department of Pharmacy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

There is a substantial lack of tacrolimus pharmacokinetic information in pediatric hematopoietic stem cell transplant (HSCT) patients. This study aimed to develop population pharmacokinetics (PopPK) of tacrolimus in pediatric HSCT patients and to devise model-guided dosage regimens. A retrospective analysis was performed on 86 pediatric HSCT patients who received tacrolimus intravenously or orally. A total of 578 tacrolimus trough concentrations (C) were available for pharmacokinetic analysis using a non-linear mixed-effects modeling method. Demographic and clinical data were included and assessed as covariates the stepwise method. Bayesian estimators were used to devise pediatric dosage regimens that targeted C of 5-15 ng mL. A one-compartment model with first-order absorption adequately described the tacrolimus pharmacokinetics. Clearance (CL), volume of distribution (V), and typical bioavailability (F) in this study were estimated to be 2.42 L h (10.84%), 79.6 L (16.51%), and 19% (13.01%), respectively. Body weight, hematocrit, post-transplantation days, and caspofungin and azoles concomitant therapy were considered significant covariates for tacrolimus CL. Hematocrit had a significant impact on the V of tacrolimus. In the subgroup cohort of children ( = 24) with genotype, the clearance was 1.38-fold higher in CYP3A5 expressers than in non-expressers. Simulation indicated that the initial dosage optimation of tacrolimus for intravenous and oral administration was recommended as 0.025 and 0.1 mg kg d (q12h), respectively. A PopPK model for tacrolimus in pediatric HSCT patients was developed, showing good predictive performance. Model-devised dosage regimens with trough tacrolimus concentrations provide a practical strategy for achieving the therapeutic range.
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http://dx.doi.org/10.3389/fphar.2022.891648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298550PMC
July 2022

Mental fatigue and negative emotion among nurses during the COVID-19 pandemic.

Curr Psychol 2022 Jul 15:1-9. Epub 2022 Jul 15.

School of Psychology, Key Laboratory of Adolescent Cyberpsychology and Behavior, Ministry of Education, Key Laboratory of Human Development and Mental Health of Hubei Province, Central China Normal University, Wuhan, China.

COVID-19 is a major public health event affecting the people worldwide. Nurses are still under immense psychological pressure. This study aimed to explore the relationship between mental fatigue and negative emotions among frontline medical staff during the COVID-19 pandemic. The study was conducted in August 2020, which included 419 medical staff between 17 to 28 years. The Fatigue Scale, Multidimensional Mental Flexibility Questionnaire, Cognitive Fusion Scale, and Depression-Anxiety-Stress Brief Version Scale were used. During the data collection period, the pandemic was under control in China and continued worldwide. The results indicated that 27.7% of the medical staff experienced depression, and 32.3% of them feel stressed. Specifically, first, correlation analyses showed significant positive pairwise correlations between mental fatigue, psychological inflexibility, cognitive fusion, and negative emotions among nurses. Second, mediation model tests showed statistically significant mediating effects of psychological inflexibility and cognitive fusion between mental fatigue on nurses' negative emotions, and statistically, significant chain mediating effects of psychological inflexibility and cognitive fusion. Mental fatigue indirectly affects nurses' negative effects through the mediating effects of psychological inflexibility, cognitive fusion, and the chain mediating effects of psychological inflexibility and cognitive fusion, respectively. the negative effects of mental fatigue come from impairment of cognitive functioning, and interventions using acceptance and commitment therapy for mental fatigue and negative emotions are more effective since both psychological inflexibility and cognitive fusion are important components of the therapy.
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http://dx.doi.org/10.1007/s12144-022-03468-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285871PMC
July 2022

Target-triggered hybridization chain reaction for ultrasensitive dual-signal miRNA detection.

Biosens Bioelectron 2022 Jul 16;215:114572. Epub 2022 Jul 16.

State Key Laboratory of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China. Electronic address:

A signal amplification sensing system with target-triggered DNA cascade reaction combined with dual-signal readout technology was designed for ultrasensitive analysis of miRNA. The highly conductive metal organic frameworks (MOFs) derivative, N-doped carbon dodecahedron (N-PCD) was deposited with gold nanoparticles as the electrode substrate, which could assist the electron transfer between the molecular probe and the electrode surface, and could remarkably enhance electrochemical response. Tetrahedral DNA nanostructure (T4-DNA) with high structural stability and mechanical stiffness was designed to improve the loading capacity and binding efficiency of the target, thus increasing the sensitivity of the system. The non-enzymatic amplification method based on the DNA cascade reaction allows the electrochemical responses from dual signal DNA probes labeled with ferrocene (Fc) and methylene blue (MB), respectively in turn to improve the reliability of detection. Under optimal conditions, the sensor has a linear range of 5-1.0 × 10 fM, and the limit of detection is as low as 1.92 fM and 3.74 fM for Fc and MB labeled probe, respectively. This strategy raises the promising application for the rapid detection of miRNA targets with low abundance in complex biological systems.
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http://dx.doi.org/10.1016/j.bios.2022.114572DOI Listing
July 2022

Inhalable dry powder mRNA vaccines based on extracellular vesicles.

Matter 2022 Jul 11. Epub 2022 Jul 11.

Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC 27607, USA.

Respiratory diseases are a global burden, with millions of deaths attributed to pulmonary illnesses and dysfunctions. Therapeutics have been developed, but they present major limitations regarding pulmonary bioavailability and product stability. To circumvent such limitations, we developed room-temperature-stable inhalable lung-derived extracellular vesicles or exosomes (Lung-Exos) as mRNA and protein drug carriers. Compared with standard synthetic nanoparticle liposomes (Lipos), Lung-Exos exhibited superior distribution to the bronchioles and parenchyma and are deliverable to the lungs of rodents and nonhuman primates (NHPs) by dry powder inhalation. In a vaccine application, severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein encoding mRNA-loaded Lung-Exos (S-Exos) elicited greater immunoglobulin G (IgG) and secretory IgA (SIgA) responses than its loaded liposome (S-Lipo) counterpart. Importantly, S-Exos remained functional at room-temperature storage for one month. Our results suggest that extracellular vesicles can serve as an inhaled mRNA drug-delivery system that is superior to synthetic liposomes.
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http://dx.doi.org/10.1016/j.matt.2022.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9272513PMC
July 2022

Recent advances in the visual detection of ions and molecules based on gold and silver nanoclusters.

Anal Methods 2022 07 29;14(29):2820-2832. Epub 2022 Jul 29.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

Gold and silver nanoclusters (Au/AgNCs) exhibit excellent application potential in optical biosensors because of their low toxicity, excellent biocompatibility, and unique optical properties. Au/AgNCs-based visual analysis methods have emerged as powerful tools for detecting various targets with convenient readout. In this review, the applications of Au/AgNCs in the visual detection and bioimaging of metal ions, inorganic anions, small molecules, and biomacromolecules in various devices are summarized. Furthermore, this review also discusses the future perspectives of the field.
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http://dx.doi.org/10.1039/d2ay00618aDOI Listing
July 2022

Cylindrical Tube Stethoscopes: The Value of Practical Equipment in the Management of Patients with Infectious Diseases.

Infect Drug Resist 2022 7;15:3611-3618. Epub 2022 Jul 7.

College of Science, Liaoning Petrochemical University, Fushun, 113001, People's Republic of China.

Background: The COVID-19 pandemic has continued for more than two years since its outbreak. Due to the clinical auscultation needs of doctors when wearing airtight protective clothing, a cylindrical tube stethoscope was proposed to address this problem. However, the idea has been questioned by some experts.

Methods: To address these questions, we performed three-part experiments using cylindrical tube stethoscopes. First, we performed laboratory tests to detect the sound intensity from a cylindrical tube stethoscope. Second, we improved the cylindrical tube stethoscope to achieve better results. Third, we revealed the difference in the auscultation effects of the cylindrical tube stethoscope and a conventional professional 3 M stethoscope.

Results: From these experiments, we found that a narrow cylindrical tube with a diameter of 4.2 cm and a length of 20 cm equipped with a silicone gasket better auscultation of heart sounds. A cylindrical tube stethoscope and a 3 M stethoscope were used to perform stethoscope tests on 10 volunteers. The alveolar lung sounds were 44.478 decibels vs 49.529 decibels, the heart sounds were 46.631 decibels vs 41.109 decibels, and the intestinal sounds were 40.132 decibels vs 43.787 decibels, respectively.

Conclusion: This improved cylindrical tube stethoscope can meet the auscultation requirements for cardiorespiratory and abdominal diagnosis during infectious disease pandemics.
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http://dx.doi.org/10.2147/IDR.S369305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273629PMC
July 2022

Lelliottia steviae sp. nov. isolated from Stevia rebaudiana Bertoni.

Arch Microbiol 2022 Jul 12;204(8):475. Epub 2022 Jul 12.

College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China.

A Gram-negative, aerobic, chemoheterotrophic, rod-shaped, and motile bacterium, designated as LST-1, was isolated from wild Stevia rebaudiana Bertoni and subjected to a polyphasic taxonomic analysis. The LST-1 strain grew optimally at 37 °C and pH 6.0-7.0 in the presence of 0.5% (w/v) NaCl. Phylogenetic analysis based on the 16S rDNA sequence indicated that LST-1 is closely related to Lelliottia jeotgali PFL01 (99.85%), Lelliottia nimipressuralis LMG10245 (98.82%), and Lelliottia amnigena LMG2784 (98.54%). Multi-locus sequence typing of concatenated partial atpD, infB, gyrB, and rpoB genes was performed to improve the resolution, and clear distinctions between the closest related type strains were observed. The results of average nucleotide identify analyses and DNA-DNA hybridization with four species (16S rDNA similarity > 98.65%) were less than 90 and 40%, respectively, verifying the distinct characteristics from other species of Lelliottia. The cellular fatty acid profile of the strain consisted of C16:0, Summed Feature3, and Summed Feature8 (possibly 16:1 w6c/16:1 w7c and 18:1 w6c) as major components. The major polar lipids included phosphatidylethanolamine, phosphatidylglycerol, an aminophospholipid, three non-characteristic phospholipids, and a non-characteristic lipid. The genome of LST-1 was 4,611,055 bp in size, with a G + C content of 55.02%. The unique combination of several phenotypic, chemotaxonomic, and genomic characteristics proved that strain LST-1 belongs to a novel species, for which the name Lelliottia steviae sp. nov. is proposed. The type strain is LST-1 (= CGMCC 1.19175 = JCM 34938).Repositories: The genbank accession numbers for the 16S rRNA gene and genome sequences of strain LST-1T are MZ497264 and CP063663, respectively.
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http://dx.doi.org/10.1007/s00203-022-03033-2DOI Listing
July 2022

Clinical Incidence and Characteristics of Newly Diagnosed Type 1 Diabetes in Chinese Children and Adolescents: A Nationwide Registry Study of 34 Medical Centers.

Front Pediatr 2022 15;10:888370. Epub 2022 Jun 15.

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

Objective: To investigate the clinical incidence and characteristics of type 1 diabetes mellitus (T1DM) of children and adolescents at the time of initial diagnosis in China.

Methods: Data on all pediatric patients with newly diagnosed T1DM were retrospectively collected from 34 medical centers in 25 major cities in China from January 2015 to January 2020. Patients were classified into three age groups: <5 years, 5 to <10 years, and ≥10 years of age. The same patient population was also categorized into diabetic ketoacidosis (DKA) and non-DKA groups based on clinical criteria.

Results: The mean annual clinical incidence of T1DM was 3.16/100,000 from the years 2015 to 2019. A total of 6,544 patients with newly diagnosed T1DM aged 0-16 years (median 7.84 ± 3.8) were studied [ages <5 years (29.3%), 5 to <10 years (38.7%), and ≥10 years (32%)], 52.4% of them were women. In total, 90.5% of the cases were occurred in individuals without a family history. Patients had lower C-peptide (CP) and body mass index (BMI) z scores when compared with healthy children, 41.8% of them had measurable T1DM-related antibodies and 52.7% had DKA. Among all three age groups, the <5 years group had the lowest BMI z score, CP, and glycated hemoglobin (HbA1c) on average, while it had the highest incidence rate of DKA (56.9%). Compared to the non-DKA group, the DKA group was significantly younger, with a lower BMI z score and CP, higher antibody positive rate, HbA1c, and the rate of insulin pump therapy.

Conclusion: The clinical incidence of T1DM in children and adolescents in China was 3.16/100,000. Patients with DKA at the first diagnosis of T1DM have a worse β-cell function. Public health measures for the prevention and treatment of T1DM should focus on preschoolers (aged <5 years) in particular, considering the severity and the highest frequency of DKA in this age group. More efforts should be dedicated to early screening and diagnosis of the T1DM.
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http://dx.doi.org/10.3389/fped.2022.888370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242427PMC
June 2022

Comparative dietary effectiveness of a modified government-recommended diet with avoidance of ultra-processed foods on weight and metabolic management in children and adolescents: An open-label, randomized study.

Asia Pac J Clin Nutr 2022 ;31(2):282-293

Departments of Endocrinology, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China. Email:

Background And Objectives: Childhood obesity is rapidly rising in China and effective diet interventions are needed. Here, we determine whether the Chinese government-recommended diet (GRD) or a modified diet of further restriction of sugar and ultra-processed food but without energy restriction, minimally processed diet (MPD) is effective on weight loss in children and adolescents with obesity/overweight.

Methods And Study Design: This open-label, randomized study included 60 children and adolescents between 5-18 years old with overweight/obesity. Participants were randomized 1:1 to the GRD or MPD and self-managed at home for 12 weeks. Both groups received general recommendations in physical activities. The changes were evaluated in body weight, fasting glucose and insulin, lipid metabolism and serum uric acid between baseline and week 12.

Results: The results indicated great reductions by time for BMI, BMI z-score, fat mass percentage and fat mass index in both groups. An obvious decrease by time for weight was found in the MPD group (p<0.001) as well as fasting glucose (p=0.005), fasting insulin (p=0.001), total cholesterol (p=0.007) and serum uric acid (p=0.006). As for the amount of visceral fat, greater reduction by time was observed in MPD group compared with GRD group.

Conclusions: A 12-week self-intervention combining the Chinese government-recommended diet with physical activities was effective on weight loss in children and adolescents with overweight/obesity. The minimally processed diet was more effective on decreasing visceral fat mass and may be beneficial to improving insulin resistance. Further studies are required to assess long-term outcomes of the general public.
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http://dx.doi.org/10.6133/apjcn.202206_31(2).0014DOI Listing
July 2022

Poor outcome of pediatric patients with acute myeloid leukemia harboring high FLT3/ITD allelic ratios.

Nat Commun 2022 06 27;13(1):3679. Epub 2022 Jun 27.

Children's Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, PR China.

Activating FLT3 mutations are the most common mutations in acute myeloid leukemia (AML), but the optimal threshold of FLT3/ITD allelic ratio (AR) among pediatric AML patients remains controversial. Here, we present the outcome and prognostic significance of FLT3/ITD AR analysis among pediatric patients with AML from the TARGET dataset. Applying fitting curve models and threshold effect analysis using the restrictive cubic spline function following Cox proportional hazards models identifies the cut-off value of 0.5 on FLT3/ITD AR. Moreover, we observe that high FLT3/ITD AR patients have an inferior outcome when compared to low AR patients. Our study also demonstrates that stem cell transplantation may improve the outcome in pediatric AML patients with high FLT3/ITD AR and may be further improved when combined with additional therapies such as Gemtuzumab Ozogamicin. These findings underline the importance of individualized treatment of pediatric AML.
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http://dx.doi.org/10.1038/s41467-022-31489-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237020PMC
June 2022

Clinical Exome Sequencing of 1000 Families with Complex Immune Phenotypes: Towards comprehensive genomic evaluations.

J Allergy Clin Immunol 2022 Jun 23. Epub 2022 Jun 23.

Bioinformatics and Computational Biosciences | Office of Cyber Infrastructure and Computational Biology.

Background: Prospective genetic evaluation of patients at our referral research hospital presents clinical research challenges.

Objective: This study sought not only a single-gene explanation for participants' immune-related presentations, but viewed each participant holistically, with the potential to have multiple genetic contributions to their immune-phenotype and other heritable comorbidities relevant to their presentation and health.

Methods: We developed a program integrating exome sequencing, chromosomal microarray, phenotyping, results return with genetic counseling, and reanalysis in 1505 individuals from 1000 families with suspected or known inborn errors of immunity.

Results: Probands were 50.8% female, 71.5% >18 years, and had diverse immune presentations. Overall, 327/1000 probands (32.7%) received 361 molecular diagnoses. These included 17 probands with diagnostic copy number variants, 32 probands with secondary findings, and 31 probands with multiple molecular diagnoses. Reanalysis added 22 molecular diagnoses, predominantly due to new disease-gene associations (9/22, 40.9%). One-quarter of the molecular diagnoses (92/361) did not involve immune-associated genes. Molecular diagnosis was correlated with younger age, male sex, and a higher number of organ systems involved. This program also facilitated the discovery of new gene-disease associations such as SASH3-related immunodeficiency. A review of treatment options and ClinGen actionability curations suggest that at least 251/361 (69.5%) of these molecular diagnoses could translate into >1 management option.

Conclusion: This program contributes to our understanding of the diagnostic and clinical utility whole exome analysis on a large scale.

Clinical: Implication: Comprehensive analysis of exome data has diagnostic and clinical utility for patients with suspected inborn errors of immunity.
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http://dx.doi.org/10.1016/j.jaci.2022.06.009DOI Listing
June 2022

Ultrafast construction of 3D ultrathin [email protected] heteronanosheet array by plasma magnetron sputtering for non-enzymatic glucose sensing in beverage and human serum.

Food Chem 2022 Nov 3;393:133399. Epub 2022 Jun 3.

College of Chemistry and Materials, Sichuan Normal University, Chengdu, Sichuan 610068, China. Electronic address:

In this work, a 3D ultra-thin NiCo-LDH nanosheet array coated Cu nanoparticles on carbon cloth ([email protected] NSA/CC) was ultrafast synthesized by plasma magnetron sputtering for the first time. This method has low toxicity and is easy to operate. As a durable and efficient 3D heteronanoarray electrocatalyst for glucose detection, [email protected] NSA/CC has higher stable conductivity and faster electron transport rate than NiCo-LDH NSA/CC and Cu nanoparticles, which work through synergistic effect to form a high-performance sensing platform. The [email protected] NSA/CC heteronanosheet structure has good electrocatalytic performance for glucose oxidation, with the sensitivity of the two linear ranges (0.001-1 mmol L and 1-6 mmol L) being 9710 μA L mmol cm and 4870 μA L mmol cm, respectively, and the detection limit (LOD) is 157 nmol L (S/N = 3). The sensor has been successfully applied to detect glucose in beverages and serum.
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http://dx.doi.org/10.1016/j.foodchem.2022.133399DOI Listing
November 2022

High Prevalence of Cardiometabolic Comorbidities Among Children and Adolescents With Severe Obesity From a Large Metropolitan Centre (Hangzhou, China).

Front Endocrinol (Lausanne) 2022 19;13:807380. Epub 2022 May 19.

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

Objective: This study aimed to describe the clinical characteristics of children and adolescents with obesity, and the prevalence of cardiometabolic comorbidities over 10 years in this population from a large metropolitan centre in China.

Methods: This was a cross-sectional study (2008-2017) of patients aged <18 years with obesity [body mass index (BMI) ≥ 95th percentile for age and sex] enrolled at the Department of Endocrinology, Children's Hospital of Zhejiang University School of Medicine (Hangzhou, Zhejiang Province). Clinical assessments included anthropometry, blood pressure, liver ultrasound, lipid profile, oral glucose tolerance test, and uric acid. For examination of outcomes, our study cohort was stratified by sex and age bands (<10 vs. ≥10 years), with the study period also split into two strata (2008-2012 and 2013-2017).

Results: A total of 2,916 patients (1,954 boys and 962 girls) were assessed at a mean age of 10.5 years. Patients almost invariably presented severe obesity (median BMI SDS = 2.98; Q1 = 2.60, Q3 = 3.39). Obesity-related comorbidities were common among boys and girls, including type 2 diabetes mellitus (2.6% and 3.6%, respectively), abnormal glycaemia (33.6% and 35.5%, respectively), hypertension (33.9% and 32.0%, respectively), dyslipidaemia (35.2% and 39.6%, respectively), hyperuricaemia (16.2% and 8.3%, respectively), acanthosis nigricans (71.9% and 64.0%, respectively), abnormal liver function (66.9% and 47.0%, respectively), and non-alcoholic fatty liver disease (NAFLD) (63.8% and 45.1%, respectively); 38.7% of boys and 44.4% of girls aged ≥10 years had metabolic syndrome. Notably, the incidence of many cardiometabolic comorbidities was in 2013-2017 compared to 2008-2012. For example, rates of hypertension among boys aged <10 years and aged ≥10 years rose from 28.4% and 26.5% to 48.0% and 35.8%, respectively, and in girls from 20.3% and 20.8% to 41.7% and 39.6%, respectively. In 2013-2017, 9.5% of girls in the older group had metabolic syndrome compared to 2.2% in 2008-2013.

Conclusions: We observed a high incidence of obesity-related cardiometabolic comorbidities among Chinese children and adolescents with severe obesity over 10 years. It was particularly concerning that rates of several comorbidities rose markedly over the study period, highlighting the need to address the obesity epidemic early in life (in China and elsewhere) to prevent the development of obesity-related comorbidities and, subsequently, of overt disease.
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http://dx.doi.org/10.3389/fendo.2022.807380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160715PMC
May 2022

Hypoxia-reinforced antitumor RNA interference mediated by micelleplexes with programmed disintegration.

Acta Biomater 2022 08 2;148:194-205. Epub 2022 Jun 2.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou 215123, China. Electronic address:

The performance of polycation-mediated siRNA delivery is often hurdled by the multiple systemic and cellular barriers that pose conflicting requirements for materials properties. Herein, micelleplexes (MPs) capable of programmed disintegration were developed to mediate efficient delivery of siRNA against XIAP (siXIAP) in a hypoxia-reinforced manner. MPs were assembled from azobenzene-crosslinked oligoethylenimine (AO), acid-transformable diblock copolymer PPDHP with conjugated photosensitizer, and siXIAP. AO efficiently condensed siXIAP via electrostatic interaction, and PPDHP rendered additional hydrophobic interaction with AO to stabilize the MPs against salt. The hydrophilic PEG corona enhanced the serum stability of MPs to prolong blood circulation and promote tumor accumulation. After internalization into cancer cells, the endolysosomal acidity triggered shedding of PPDHP, exposing AO to induce endolysosomal escape. Then, light irradiation generated lethal amount of ROS, and concurrently aggravated intracellular hypoxia level to degrade AO into low-molecular weight segments, release siXIAP, and potentiate the XIAP silencing efficiency. Thus, siXIAP-mediated pro-apoptosis cooperated with generated ROS to provoke pronounced anti-cancer efficacy against Skov-3 tumors in vitro and in vivo. This study provides a hypoxia-instructed strategy to overcome the multiple barriers against anti-cancer siRNA delivery in a programmed manner. STATEMENT OF SIGNIFICANCE: The success of RNA interference (RNAi) heavily depends on delivery systems that can enable spatiotemporal control over siRNA delivery. Herein, we developed micelleplexes (MPs) constructed from hypoxia-degradable, azobenzene-crosslinked oligoethylenimine (AO) and acid-responsive, photosensitizer-conjugated diblock copolymer PPDHP, to mediate efficient anti-tumor siRNA (siXIAP) delivery via programmed disintegration. MPs possessed high salt/serum stability and underwent acid-triggered PPDHP detachment to promote endolysosomal escape. Then, light irradiation aggravated hypoxia to trigger AO degradation and intracellular siXIAP release, which cooperated with photodynamic therapy to eradicate tumor cells. This study presents a new example of hypoxia-degradable polycation to mediate hypoxia-reinforced RNAi, and it also renders an effective strategy to overcome the complicated extracellular/intracellular barriers against systemic siRNA delivery.
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http://dx.doi.org/10.1016/j.actbio.2022.05.050DOI Listing
August 2022

The Association Between Food Addiction and Weight Status in School-Age Children and Adolescents.

Front Psychiatry 2022 9;13:824234. Epub 2022 May 9.

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

Background: The association between food addiction (FA) and weight status in children and adolescents remains poorly understood. This study aimed to elucidate the association between FA and weight status using the validated Chinese version of the dimensional Yale Food Addiction Scale for Children 2.0 (dYFAS-C 2.0).

Methods: Participants were enrolled from clinic visitors for regular physical check in a children's hospital. The dYFAS-C 2.0 was translated into Chinese and validated using reliability and validity tests. The participants' body mass index score (BMIZ) and waist-to-height ratio (WHtR) were used to characterize weight status. The FA severity was assessed using the translated dYFAS-C 2.0.

Results: Among the 903 children and adolescents enrolled, 426 (47.2%) completed the survey [277 (65%) females and 149 (35%) males]. The Cronbach α of translated dYFAS-C 2.0 was 0.934, and confirmatory factor analysis indicated an acceptable model fit. FA correlated positively with BMIZ and WHtR in the whole sample after adjusting for the effect of gender ( < 0.001). Further analyses showed that the correlation remained significant in participants with BMIZ > 1 ( = 0.006) but not in those with BMIZ ≤ 1 ( = 0.220). However, the correlations between FA and WHtR were statistically significant in both participants with or without abdominal obesity ( < 0.05). The FA could explain 12.1 and 15.8% of variance in BMIZ and WHtR, respectively. The corresponding cutoff points of FA for excessive weight risk were 0.7 (BMIZ) and 0.4 (WHtR).

Conclusion: The dYFAS-C 2.0 has good reliability and validity in the Chinese population. FA is associated with weight status characterized by BMIZ and WHtR, especially in participants with BMIZ > 1 and in those with abdominal obesity.

Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR2100052239].
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http://dx.doi.org/10.3389/fpsyt.2022.824234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125319PMC
May 2022

A New Generation of Lineage Tracing Dynamically Records Cell Fate Choices.

Int J Mol Sci 2022 Apr 30;23(9). Epub 2022 Apr 30.

Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, China.

Reconstructing the development of lineage relationships and cell fate mapping has been a fundamental problem in biology. Using advanced molecular biology and single-cell RNA sequencing, we have profiled transcriptomes at the single-cell level and mapped cell fates during development. Recently, CRISPR/Cas9 barcode editing for large-scale lineage tracing has been used to reconstruct the pseudotime trajectory of cells and improve lineage tracing accuracy. This review presents the progress of the latest CbLT (CRISPR-based Lineage Tracing) and discusses the current limitations and potential technical pitfalls in their application and other emerging concepts.
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http://dx.doi.org/10.3390/ijms23095021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105840PMC
April 2022

Multimodal Human-Exoskeleton Interface for Lower Limb Movement Prediction Through a Dense Co-Attention Symmetric Mechanism.

Front Neurosci 2022 25;16:796290. Epub 2022 Apr 25.

School of Automation Engineering, University of Electronic Science and Technology of China, Chengdu, China.

A challenging task for the biological neural signal-based human-exoskeleton interface is to achieve accurate lower limb movement prediction of patients with hemiplegia in rehabilitation training scenarios. The human-exoskeleton interface based on single-modal biological signals such as electroencephalogram (EEG) is currently not mature in predicting movements, due to its unreliability. The multimodal human-exoskeleton interface is a very novel solution to this problem. This kind of interface normally combines the EEG signal with surface electromyography (sEMG) signal. However, their use for the lower limb movement prediction is still limited-the connection between sEMG and EEG signals and the deep feature fusion between them are ignored. In this article, a Dense con-attention mechanism-based Multimodal Enhance Fusion Network (DMEFNet) is proposed for predicting lower limb movement of patients with hemiplegia. The DMEFNet introduces the con-attention structure to extract the common attention between sEMG and EEG signal features. To verify the effectiveness of DMEFNet, an sEMG and EEG data acquisition experiment and an incomplete asynchronous data collection paradigm are designed. The experimental results show that DMEFNet has a good movement prediction performance in both within-subject and cross-subject situations, reaching an accuracy of 82.96 and 88.44%, respectively.
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http://dx.doi.org/10.3389/fnins.2022.796290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9082753PMC
April 2022

Peptide PDHPS1 Inhibits Ovarian Cancer Growth through Disrupting YAP Signaling.

Mol Cancer Ther 2022 07;21(7):1160-1170

Department of Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, China.

The lives of patients with ovarian cancer are threatened largely due to metastasis and drug resistance. Endogenous peptides attract increasing attention in oncologic therapeutic area, a few antitumor peptides have been approved by the FDA for clinical use over the past decades. However, only few peptides or peptide-derived drugs with antiovarian cancer effects have been identified. Here we focused on the biological roles and mechanism of a peptide named PDHPS1 in ovarian cancer development. Our results indicated that PDHPS1 reduced the proliferation ability of ovarian cancer cells in vitro and inhibited the ovarian cancer growth in vivo. Peptide pull down and following mass spectrometry, Western blot and qRT-PCR revealed that PDHPS1 could bind to protein phosphatase 2 phosphatase activator (PTPA), an essential activator of protein phosphatase 2A (PP2A), which resulted in increase of phosphorylated YAP, further inactivated YAP, and suppressed the expression of its downstream target genes. Flow cytometry, cell membrane permeability test, and IHC staining study demonstrated that there were no observable side effects of PDHPS1 on normal ovarian epithelium and hepatorenal function. Besides, modification of membrane penetration could improve the physicochemical properties and biological activity of PDHPS1. In conclusion, our study demonstrated that the endogenous peptide PDHPS1 serves as an antitumor peptide to inhibit YAP signaling pathway though interacting with PTPA in ovarian cancer.
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http://dx.doi.org/10.1158/1535-7163.MCT-21-0848DOI Listing
July 2022

Minimally invasive delivery of a hydrogel-based exosome patch to prevent heart failure.

J Mol Cell Cardiol 2022 Aug 2;169:113-121. Epub 2022 Jun 2.

Division of Cardiothoracic Surgery, the University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address:

Coronary heart disease (CHD) has been the number one killer in the United States for decades and causes millions of deaths each year. Clinical treatment of heart ischemic injury relieves symptoms in the acute stage of CHD; however, patients with an infarcted heart muscle can develop heart failure (HF) due to chronic maladaptive remodeling. Regenerative therapy has been studied as a potential treatment option for myocardial infarction (MI) and HF. Cardiac patches have been designed and tested to increase therapeutic retention and integration. However, the delivery usually requires invasive surgical techniques, including open-chest surgeries and heart manipulation. Those procedures may cause chronic adhesions between the heart anterior wall and the chest wall. This study created and tested an injectable ExoGel by embedding mesenchymal stem cell (MSC) -derived exosomes into a hyaluronic acid (HA) hydrogel. ExoGel was injected into the pericardial cavity of rats with transverse aortic constriction (TAC) induced heart failure. ExoGel therapy reduced LV chamber size and preserved wall thickness. The feasibility and safety of ExoGel injection were further confirmed in a pig model.
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http://dx.doi.org/10.1016/j.yjmcc.2022.04.020DOI Listing
August 2022

Evaluation of Essential and Toxic Elements in the Blood of 0-14-Year-Old Children in Hunan, China From 2013 to 2019: A Retrospective Analysis.

Front Public Health 2022 18;10:739880. Epub 2022 Apr 18.

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

Objective: The aim was to investigate the distribution and correlation of Ca, Mg, Zn, Cu, Fe, Pb, and Cd in the blood of children aged 0-14 years in Hunan, China, which may serve to provide a basis for clinical guidance on child health.

Study Design: A retrospective analysis was carried out. Concentrations of all elements were determined by atomic absorption spectrophotometry. Distributions were analyzed and compared among different age, sex, and year groups by the Kruskal-Wallis test, the chi-square test, and the Fisher's exact test. Spearman's rank correlation coefficient was used to evaluate the association between every pair of elements.

Results: A total of 46,951 children were involved in this study from 2013 to 2019. The median blood levels of elements were 13.51 μmol/L (Cu), 58.69 μmol/L (Zn), 1.70 mmol/L (Ca), 1.40 mmol/L (Mg), 7.46 mmol/L (Fe), 35.00 μg/L (Pb), and 1.00 μg/L (Cd). Girls had a higher level of Ca and lower levels of Pb and Cd than boys. Cu and Ca showed an upward trend, and Mg and Pb showed a downward trend by year. Zn and Fe increased and Ca decreased significantly with age. The deficiency rates of Fe and Zn decreased significantly by year, while Ca and Cu increased significantly by year. Cd exposure in this area was relatively low.

Conclusion: Most children had normal levels of the essential elements Ca, Cu, and Mg and the toxic elements Pb and Cd. Severe deficiencies in Zn and Fe were observed in the relatively younger children but improved with age. Persistent efforts in reducing Pb exposure might still be needed.
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http://dx.doi.org/10.3389/fpubh.2022.739880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058121PMC
May 2022

GFI1 regulates chromatin state essential in human endothelial-to-haematopoietic transition.

Cell Prolif 2022 May 3;55(5):e13244. Epub 2022 May 3.

CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

Objectives: During embryonic haematopoiesis, haematopoietic stem/progenitor cells (HSPCs) develop from hemogenic endothelial cells (HECs) though endothelial to haematopoietic transition (EHT). However, little is known about how EHT is regulated in human. Here, we report that GFI1 plays an essential role in enabling normal EHT during haematopoietic differentiation of human embryonic stem cells (hESCs).

Results: GFI1 deletion in hESCs leads to a complete EHT defect due to a closed chromatin state of hematopoietic genes in HECs. Mechanically, directly regulates important signaling pathways essential for the EHT such as PI3K signaling.etc.

Conclutions: Together, our findings reveal an essential role of GFI1 mediated epigenetic mechanism underlying human EHT during hematopoiesis.
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http://dx.doi.org/10.1111/cpr.13244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136496PMC
May 2022

Integrated analysis of mRNA and long noncoding RNA profiles in peripheral blood mononuclear cells of patients with bronchial asthma.

BMC Pulm Med 2022 May 2;22(1):174. Epub 2022 May 2.

Department of Pathophysiology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Background: Bronchial asthma is a heterogeneous disease with distinct disease phenotypes and underlying pathophysiological mechanisms. Long non-coding RNAs (lncRNAs) are involved in numerous functionally different biological and physiological processes. The aim of this study was to identify differentially expressed lncRNAs and mRNAs in patients with asthma and further explore the functions and interactions between lncRNAs and mRNAs.

Methods: Ten patients with asthma and 9 healthy controls were enrolled in this study. RNA was isolated from peripheral blood mononuclear cells. We performed microarray analysis to evaluate lncRNA and mRNA expression. The functions of the differentially expressed mRNAs were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. A global signal transduction network was constructed to identify the core mRNAs. An lncRNA-mRNA network was constructed. Five mRNAs showing the greatest differences in expression levels or high degrees in the gene-gene functional interaction network, with their correlated lncRNAs, were validated by real-time quantitative polymerase chain reaction.

Results: We identified 2229 differentially expressed mRNAs and 1397 lncRNAs between the asthma and control groups. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified many pathways associated with inflammation and cell survival. The gene-gene functional interaction network suggested that some core mRNAs are involved in the pathogenesis of bronchial asthma. The lncRNA-mRNA co-expression network revealed correlated lncRNAs. CXCL8, FOXO3, JUN, PIK3CA, and G0S2 and their related lncRNAs NONHSAT115963, AC019050.1, MTCYBP3, KB-67B5.12, and HNRNPA1P12 were identified according to their differential expression levels and high degrees in the gene-gene network.

Conclusions: We identified the core mRNAs and their related lncRNAs and predicted the biological processes and signaling pathways involved in asthma.
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http://dx.doi.org/10.1186/s12890-022-01945-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9059365PMC
May 2022
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