Publications by authors named "Jian Xu"

2,423 Publications

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Mechanisms of stress response in the root stem cell niche.

J Exp Bot 2021 Jun 10. Epub 2021 Jun 10.

Institute of Cytology and Genetics, Novosibirsk, Russia.

As plants are sessile organisms unable to escape from environmental hazards, they need to adapt for survival. The stem cell niche in the root apical meristem is particularly sensitive to DNA damage induced by environmental stresses such as chilling, flooding, wounding, UV, and irradiation. DNA damage has been proven to cause stem cell death, with stele stem cells being the most vulnerable. Stress also induces the division of quiescent center cells. Both reactions disturb the structure and activity of the root stem cell niche temporally; however, this preserves root meristem integrity and functioning long-term. Plants have evolved many mechanisms that ensure stem cell niche maintenance, recovery, and acclimation, allowing them to survive in a changing environment. Here, we give an overview of the cellular and molecular aspects of stress responses in the root stem cell niche.
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http://dx.doi.org/10.1093/jxb/erab274DOI Listing
June 2021

Predicting Risk of Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus: CSTAR Cohort Study.

Arthritis Rheumatol 2021 Jun 9. Epub 2021 Jun 9.

Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Objectives: Pulmonary arterial hypertension is a life-threatening complication of systemic lupus erythematosus. However, there is no algorithm to identify those at high risk. We aimed to develop a prediction model for pulmonary arterial hypertension in lupus patients that provides individualized risk estimates.

Methods: A multicenter, longitudinal cohort study was undertaken from January 2003 to January 2020. The study collected data on 3,624 consecutively evaluated patients diagnosed with lupus. The diagnosis of pulmonary arterial hypertension was confirmed by right heart catheterization. Cox proportional hazards regression and least absolute shrinkage and selection operator were used to fit the model. Model discrimination, calibration, and decision curve analysis were assessed for validation.

Results: Ninety-two lupus patients developed pulmonary arterial hypertension (2.54%) at a median follow-up of 4.84 years (interquartile range, 2.42-8.84). The final prediction model included five clinical variables (acute/subacute cutaneous lupus, arthritis, renal disorder, thrombocytopenia, and interstitial lung disease) and three autoantibodies (anti-RNP, anti-Ro/SSA and anti-La/SSB). A 10-year pulmonary arterial hypertension probability-predictive nomogram was established. The model was internally validated by C statistic (0.78), the Brier score (0.03), and a satisfactory calibration curve. According to the net benefit and predicted probability thresholds, we recommend annual screening in high-risk (> 4.62 %) lupus patients.

Conclusion: We developed a risk stratification model using routine clinical assessments. This new tool may effectively predict the future risk of pulmonary arterial hypertension in patients with systemic lupus erythematosus.
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http://dx.doi.org/10.1002/art.41740DOI Listing
June 2021

Neuroprotective Activities of Constituents from Phyllosticta capitalensis, an Endophyte Fungus of Loropetalum chinense var. rubrum.

Chem Biodivers 2021 Jun 8. Epub 2021 Jun 8.

China Pharmaceutical University, Department of Natural Medicinal Chemistry, China Pharmaceutical University Xuanwumen Campus, No.24, Tongjiaxiang, Gulou Dis, China Pharmaceutical University Jiangning Campus, No.639,Longmiandadao, Jiangnin, 210009, Nanjing, CHINA.

One new dioxolanone derivative, guignardianone G ( 1 ) and twelve known compounds ( 2 - 13 ) were isolated from the 95% ethanol extract of the plant endophytic fungus Phyllosticta capitalensis cultured in rice medium. Among the known compounds isoaltenuene ( 3 ), brassicasterol ( 7 ), 5,6-epoxyergosterol ( 8 ), citreoanthrasteroid A ( 9 ), demethylincisterol A ( 10 ), chaxine C ( 11 ) were reported from Phyllosticta sp. for the first time. The structures of 1 was elucidated by 1D- and 2D-NMR experiments and HR-ESI-MS data analysis, and its absolute configuration was established through the comprehensive use of the methods of modified Mosher methods, calculations of ECD spectra and optical rotation values. The neuroprotective activity of compounds 1 - 9 , 11 - 13 were evaluated on PC12 cells damage induced by glutamate, and compounds 9 and 12 showed potential neuroprotective activities and compounds 9 and 12 with half effective concentration (EC 50 ) of 24.2 and 33.9 μ M, respectively.
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http://dx.doi.org/10.1002/cbdv.202100314DOI Listing
June 2021

Fascin promotes the invasion of pituitary adenoma through partial dependence on epithelial-mesenchymal transition.

J Mol Histol 2021 Jun 7. Epub 2021 Jun 7.

Department of Neurosurgery, The First Affiliated Hospital, Shihezi University School of Medicine, North 2 Road, Shihezi, 832000, Xinjiang, China.

The aim of the present study was to investigate the role and potential regulatory mechanisms of fascin in the invasion and epithelial-to-mesenchymal transition of pituitary adenoma cells. A total of 30 specimens were assessed in the present study. The expression levels of fascin in the invasive pituitary adenoma group and non-invasive pituitary adenoma group were determined by immunochemistry. Fascin was downregulated via small interfering RNA in mouse pituitary AtT-20 cells. The proliferation, cell cycle and apoptosis of AtT-20 cells were assessed using Cell Counting Kit‑8 and flow cytometry. The invasion of AtT-20 cells was detected using a Transwell assay. Transmission electron microscopy was utilized to observe the ultrastructure of AtT-20 cells. Real-time quantitative PCR, Western blotting and immunofluorescence staining were utilized to detect the expression levels of fascin and EMT markers. In the present study, fascin expression and clinical characteristics were not significantly correlated in pituitary adenoma. The protein expression level of fascin in invasive pituitary adenoma was higher than that in non-invasive pituitary adenoma, as assessed by immunochemistry. Downregulation of fascin resulted in significant decreases in cell viability, proliferation and invasion, arrested the cell cycle at the G1 phase and increased apoptosis. In addition, downregulation of fascin significantly decreased the expression levels of N-cadherin, the mesenchymal cell marker vimentin and the transcription factor Twist but significantly increased the expression levels of the epithelial cell marker E-cadherin. Further experiments revealed that overexpression of E-cadherin resulted in significant decreases in cell viability, proliferation, invasion, and the expression of fascin and transcription factor Twist and also arrested the cell cycle at the G2 phase. The results of the present study suggest that suppressing the expression level of fascin could regulate the invasion, proliferation and apoptosis of pituitary tumour cells and alter the expression level of various EMT markers. The present study identified that fascin effectively promotes the invasion, proliferation and apoptosis of pituitary tumour cells partially via the EMT pathway.
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http://dx.doi.org/10.1007/s10735-021-09995-9DOI Listing
June 2021

ICI plus chemotherapy prolonged survival over ICI alone in patients with previously treated advanced NSCLC.

Cancer Immunol Immunother 2021 Jun 7. Epub 2021 Jun 7.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, No. 507, Zheng Min Road, Shanghai, 200433, People's Republic of China.

Objectives: Immune checkpoint inhibitors (ICI) monotherapy was standard of care in second-line treatment of patients with advance non-small cell lung cancer (NSCLC). This study aims to investigate the efficacy of ICI plus chemotherapy in patients with previously treated advanced NSCLC.

Patients And Methods: An investigator-initiated trial (IIT) aiming to evaluate the efficacy and safety of ICI in combination with chemotherapy as second line and beyond for patients with advanced NSCLC was undergone at Shanghai Pulmonary Hospital (ChiCTR1900026203). Patients who received ICI monotherapy as second or later line setting during the same period were also collected as a comparator.

Results: From April 2018 to June 2019, 31 patients were included into this IIT study, simultaneously 51 patients treated with ICI monotherapy were selected as a comparator. ICI plus chemotherapy showed a significantly higher ORR (35.5% vs. 15.7%, p=0.039), prolonged PFS (median: 5.6 vs. 2.5 months, p = 0.013) and OS (median: NE vs. 12.6 months, p = 0.038) compared with ICI alone. In the subgroup of negative PD-L1 expression (9 patients in combination group and 12 patients in monotherapy group), ICI plus chemotherapy also had a favorable ORR (44.4% vs. 8.3%, p = 0.119), longer PFS (median: 6.5 vs 3.0 months, p < 0.05) and OS (median: NE vs. 8.2 months, p = 0.117). Meanwhile, the addition of chemotherapy did not increase immune-related adverse events.

Conclusions: ICI plus chemotherapy showed superior ORR, PFS and OS than ICI alone patients with previous treated advanced NSCLC. These findings warrant further investigation.
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http://dx.doi.org/10.1007/s00262-021-02974-9DOI Listing
June 2021

Identification of Mamu-DRB1 gene as a susceptibility factor for Entamoeba nuttalli infection in Chinese Macaca mulatta.

Infect Genet Evol 2021 Jun 6;93:104952. Epub 2021 Jun 6.

Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address:

Entamoeba nuttalli infection is highly prevalent in captive and wild macaques. A recent study suggested that the genetic factor of host macaques was correlated with the genotypes of E. nuttalli isolates. This study focused on the correlation between the rhesus macaque host major histocompatibility complex gene and E. nuttalli infection. Thirty-nine stool samples were obtained from Mount Qing-ling (Guizhou Province, China). Polymerase chain reaction analysis detected the infection rate of E. nuttalli, Entamoeba coli, and Entamoeba chattoni as 69.23%, 69.23%, and 87.18%, respectively. A new Serine-rich Protein genotype was detected, and the rRNA of E. nuttalli isolates from Mount Qian-ling was completely identical to the GY4 strain. In the distance-based neighbor-joining tree, Mamu-DRB1, not Mamu-DPB or Mamu-B gene, was related to E. nuttalli infection. Mamu-DRB1 genes of rhesus macaques in Mounts Qian-ling and Long-hu were highly polymorphic, and the rhesus macaques with two major types of Mamu-DRB1 showed susceptibility to E. nuttalli infection. The Mamu-DRB1 gene analysis in this study indicated that the Mamu-DRB1 gene is an important factor that influences the susceptibility of E. nuttalli infection in Chinese Macaca mulatta. This study contributes to a better understanding of host susceptibility to Entamoeba.
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http://dx.doi.org/10.1016/j.meegid.2021.104952DOI Listing
June 2021

Prenatal prediction and typing of placental invasion using MRI deep and radiomic features.

Biomed Eng Online 2021 Jun 5;20(1):56. Epub 2021 Jun 5.

Faculty of Electrical Engineering and Computer Science, Ningbo University, Ningbo, 315211, Zhejiang, China.

Background: To predict placental invasion (PI) and determine the subtype according to the degree of implantation, and to help physicians develop appropriate therapeutic measures, a prenatal prediction and typing of placental invasion method using MRI deep and radiomic features were proposed.

Methods: The placental tissue of abdominal magnetic resonance (MR) image was segmented to form the regions of interest (ROI) using U-net. The radiomic features were subsequently extracted from ROI. Simultaneously, a deep dynamic convolution neural network (DDCNN) with codec structure was established, which was trained by an autoencoder model to extract the deep features from ROI. Finally, combining the radiomic features and deep features, a classifier based on the multi-layer perceptron model was designed. The classifier was trained to predict prenatal placental invasion as well as determine the invasion subtype.

Results: The experimental results show that the average accuracy, sensitivity, and specificity of the proposed method are 0.877, 0.857, and 0.954 respectively, and the area under the ROC curve (AUC) is 0.904, which outperforms the traditional radiomic based auxiliary diagnostic methods.

Conclusions: This work not only labeled the placental tissue of MR image in pregnant women automatically but also realized the objective evaluation of placental invasion, thus providing a new approach for the prenatal diagnosis of placental invasion.
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http://dx.doi.org/10.1186/s12938-021-00893-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180077PMC
June 2021

Magnetic mesoporous embolic microspheres in transcatheter arterial chemoembolization for liver cancer.

Acta Biomater 2021 May 31. Epub 2021 May 31.

Department of Interventional Therapy, Department of Radiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002, Jiangsu, P.R. China; College of Medical Imaging, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, P.R. China. Electronic address:

Transcatheter arterial chemoembolization (TACE) is the main treatment for liver cancer. Although many embolic agents have been exploited in TACE, embolic agents combining embolization, drug loading, and imaging properties have not yet been constructed. Herein, we report a new magnetic mesoporous embolic microsphere that can simultaneously be loaded with doxorubicin (Dox), block vessels, and be observed by magnetic resonance imaging (MRI). The microspheres were prepared by decorating magnetic polystyrene/Fe3O4 particles with mesoporous organosilica microparticles (denoted as PS/[email protected]). The PS/[email protected] were uniformly spherical and large (50 μm), with a high specific surface area, uniform mesopores, and a Dox loading capacity of 460.8 μg mg-1. Dox-loaded PS/[email protected] (PS/[email protected]@Dox) effectively inhibited liver cancer cell growth. A VX2 rabbit liver tumor model was constructed to study the efficacy of TACE with PS/[email protected]@Dox. In vivo, PS/[email protected]@Dox could be smoothly delivered through an arterial catheter to achieve chemoembolization. Moreover, PS/[email protected]@Dox and residual tumor parenchyma could be distinguished on MRI, which is of great significance for evaluating the efficacy of TACE. Histopathology showed that PS/[email protected]@Dox could be deposited in the tumor vessels, completely blocking the blood supply. Overall, PS/[email protected]@Dox showed good drug loading, embolization and imaging performance as well as potential for use in TACE. STATEMENT OF SIGNIFICANCE: : Transcatheter arterial chemoembolization (TACE) is the main treatment for liver cancer. Although many embolic agents have been exploited in TACE, embolic agents combining embolization, drug-loading, and imaging properties have not yet been constructed. In this work, we prepared magnetic mesoporous microspheres as a new embolic agent that can simultaneously load doxorubicin (Dox), block blood vessels and enable magnetic resonance imaging. Overall, this new embolic microsphere-mediated TACE strategy for liver cancer showed good therapeutic effects, and the PS/[email protected]@Dox embolic microspheres provide a new avenue for improving the efficacy of TACE for liver cancer and postoperative evaluation.
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http://dx.doi.org/10.1016/j.actbio.2021.05.031DOI Listing
May 2021

Occurrence, bioaccumulation and toxicological effect of drugs of abuse in aquatic ecosystem: A review.

Environ Res 2021 May 26;200:111362. Epub 2021 May 26.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China; State Environmental Protection Key Laboratory of Ecological Effect and Risk Assessment of Chemicals, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China. Electronic address:

Drugs of abuse are a group of emerging contaminants. As the prevalence of manufacture and consumption, there is a growing global environmental burden and ecological risk from the continuous release of these contaminants into environment. The widespread occurrence of drugs of abuse in waste wasters and surface waters is due to the incomplete removal through traditional wastewater treatment plants in different regions around the world. Although their environmental concentrations are not very high, they can potentially influence the aquatic organisms and ecosystem function. This paper reviews the occurrence of drugs of abuse and their metabolites in waste waters and surface waters, their bioaccumulation in aquatic plants, fishes and benthic organisms and even top predators, and the toxicological effects such as genotoxic effect, cytotoxic effect and even behavioral effect on aquatic organisms. In summary, drugs of abuse occur widely in aquatic environment, and may exert adverse impact on aquatic organisms at molecular, cellular or individual level, and even on aquatic ecosystem. It necessitates the monitoring and risk assessment of these compounds on diverse aquatic organisms in the further study.
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http://dx.doi.org/10.1016/j.envres.2021.111362DOI Listing
May 2021

Production of butanol from distillers' grain waste by a new aerotolerant strain of Clostridium beijerinckii LY-5.

Bioprocess Biosyst Eng 2021 May 27. Epub 2021 May 27.

Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, School of Food and Biological Engineering, Hubei University of Technology, 28 Nanli Road, Wuhan, 430068, China.

A new aerotolerant strain of Clostridium beijerinckii LY-5 was isolated from the pit mud of the Chinese Baijiu-making process for butanol production. Plackett-Burman design and artificial neural network were used to optimize the fermentation medium and a total of 13.54 ± 0.22 g/L butanol and 19.91 ± 0.52 g/L ABE were attained under aerotolerant condition. Moreover, distillers' grain waste (DGW), the main by-product in the Baijiu production process, was utilized as potential substrate for butanol production. DGW was hydrolyzed by α-amylase and glucoamylase and then fermented after a detoxifying process of overliming. Butanol and ABE concentrations were 9.02 ± 0.18 and 9.57 ± 0.19 g/L with the yield of 0.21 and 0.23 g/g sugar, respectively. The higher ratio of butanol to ABE might be caused by the inhibitors in DGW medium affecting the metabolic pathways of C. beijerinckii LY-5 and approximately 1.48 ± 0.04 g/L isopropanol was found at the end of fermentation. This work highlights the feasibility of using DGW as a promising feedstock for butanol production by a new aerotolerant strain of C. beijerinckii LY-5, with benefit to the environment.
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http://dx.doi.org/10.1007/s00449-021-02592-wDOI Listing
May 2021

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

mSystems 2021 May 27: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
May 2021

SIRT1 regulates sphingolipid metabolism and neural differentiation of mouse embryonic stem cells through c-Myc- SMPDL3B.

Elife 2021 May 27;10. Epub 2021 May 27.

Signal Transduction Laboratory, National Institute of Environmental Health Sciences, RTP, United States.

Sphingolipids are important structural components of cell membranes and prominent signaling molecules controlling cell growth, differentiation, and apoptosis. Sphingolipids are particularly abundant in the brain, and defects in sphingolipid degradation are associated with several human neurodegenerative diseases. However, molecular mechanisms governing sphingolipid metabolism remain unclear. Here we report that sphingolipid degradation is under transcriptional control of SIRT1, a highly conserved mammalian NAD-dependent protein deacetylase, in mouse embryonic stem cells (mESCs). Deletion of SIRT1 results in accumulation of sphingomyelin in mESCs, primarily due to reduction of SMPDL3B, a GPI-anchored plasma membrane bound sphingomyelin phosphodiesterase. Mechanistically, SIRT1 regulates transcription of through c-Myc. Functionally, SIRT1 deficiency-induced accumulation of sphingomyelin increases membrane fluidity and impairs neural differentiation and . Our findings discover a key regulatory mechanism for sphingolipid homeostasis and neural differentiation, further imply that pharmacological manipulation of SIRT1-mediated sphingomyelin degradation might be beneficial for treatment of human neurological diseases.
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http://dx.doi.org/10.7554/eLife.67452DOI Listing
May 2021

Occurrence of pharmaceuticals and personal care products in bottled water and assessment of the associated risks.

Environ Int 2021 May 23;155:106651. Epub 2021 May 23.

College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, China Agricultural University, Beijing 100193, China. Electronic address:

The occurrence of 187 pharmaceuticals and personal care products (PPCPs) was investigated in bottled water samples (35 and 33 from Chinese and foreign brands, respectively). Forty-four compounds belonging to 14 PPCP categories were detected in 56 of the 68 bottled water samples. Further, more than 35% of water samples contained at least three PPCPs, and in one particular sample, 11 different PPCPs were detected. Macrolides constituted the most prevalent PPCP category, and salbutamol, erythromycin, and azithromycin showed the highest detection frequency (17.6%). The thermal stabilities of the 187 PPCPs were determined, and the results obtained showed that only 35 out of the 187 compounds were degraded by more than 50% after boiling for 5 min. Even though the risk quotients (RQs) of detected PPCPs showed low risk levels, the RQs of 13 compounds with RQs ≥ 0.0001 were 2-4 fold higher in infants than in other life stages. Moreover, further studies are necessary to evaluate the toxicity of PPCP mixtures, the effects of PPCPs on human intestinal microbiota, and their risk of induction of drug-resistant bacteria and drug-resistant genes.
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http://dx.doi.org/10.1016/j.envint.2021.106651DOI Listing
May 2021

Genetic disruption of Grm5 causes complex alterations in motor activity, anxiety and social behaviors.

Behav Brain Res 2021 May 21;411:113378. Epub 2021 May 21.

Department of Physiology, Northwestern University Feinberg School of Medicine, United States; Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Chicago, IL, 60611, United States. Electronic address:

Autism is a neurodevelopmental disorder characterized by impaired social interactions and restricted and repetitive behaviors. Although group 1 metabotropic glutamate receptors (mGluRs), and in particular mGluR5, have been extensively proposed as potential targets for intervention in autism and other neurodevelopmental disorders, there has not been a comprehensive analysis of the effect of mGluR5 loss on behaviors typically assessed in autism mouse models thought to be correlates of behavioral symptoms of human disorders. Here we present a behavioral characterization of mice with complete or partial loss of mGluR5 (homozygous or heterozygous null mutations in Grm5 gene). We tested several autism related behaviors including social interaction, repetitive grooming, digging and locomotor behaviors. We found that digging and marble burying behaviors were almost completely abolished in mGluR5 ko mice, although self-grooming was not altered. Social interaction was impaired in ko but not in heterozygote (het) mice. In tests of locomotor activity and anxiety related behaviors, mGluR5 ko mice exhibited hyperactivity and reduced anxiety in the open field test but unexpectedly, showed hypoactivity in the elevated zero-maze test. There was no impairment in motor learning in the accelerating rotarod in both ko and het mutant. Together these results provide support for the importance of mGluR5 in motor and social behaviors that are specifically affected in autism disorders.
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http://dx.doi.org/10.1016/j.bbr.2021.113378DOI Listing
May 2021

Correlative research of the incidence of preeclampsia and sperm exposure.

Arch Gynecol Obstet 2021 May 23. Epub 2021 May 23.

Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, Zhejiang, China.

Purpose: This study aimed to evaluate the incidence of preeclampsia after a long duration or a short duration of sperm exposure with the biological father.

Methods: Analyze the clinical and follow-up data of 502 single birth primigravid women in Women's Hospital, School of Medicine, Zhejiang University. They were divided into two groups according to the duration of sperm exposure with the biological father, short duration of sperm exposure (≤ 3 months) and long duration of sperm exposure (≥ 12 months). Basic information and clinical characteristics in each group were evaluated.

Results: A total of 502 patients were followed, included 122 long duration of sperm exposure and 380 short duration of sperm exposure. Patients in the long duration group were younger than the short group (aged 31.49 ± 3.21 vs 27.49 ± 3.21 years, P < 0.001). These two groups had no statistical significant in patient's body mass index, education level, gestational age, birth weight, fetal birth weight, fetal sex and delivery mode (P > 0.05). Stratified analysis with the cutoff of 30 year-old suggested that the incidence of pregnancy-induced hypertension (PIH)/preeclampsia (PE) of short duration group was significantly higher than the long duration group (OR 2.82; 95% CI 1.08-7.41), so as PE (OR 10.28; 95% CI 1.01-105.02). Stratified analysis suggested no significantly increased or decreased risk for PIH (OR 1.59; 95% CI 0.54-4.68), gestational diabetes mellitus (OR 0.6; 95% CI 0.31-1.18), intrahepatic cholestasis of pregnancy (OR 2.49; 95% CI 0.34-18.48) or fetal anomaly (OR 0.4; 95% CI 0.14-1.20).

Conclusion: A long duration of sperm exposure with the biological father may reduce the incidence of PE.
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http://dx.doi.org/10.1007/s00404-021-06100-zDOI Listing
May 2021

DFT study of the fouling deposition process in the steam generator by simulating the adsorption of Fe on FeO (0 0 1).

J Mol Model 2021 May 21;27(6):175. Epub 2021 May 21.

School of Materials, Sun Yat-sen University, No.132, Outer-Ring East Road, Guangzhou, 510006, People's Republic of China.

In order to reveal the fouling problem on the outer surface of the steam generator (SG) tube in the secondary circuit condition of pressurized water reactor (PWR) nuclear power plant, based on the density functional theory (DFT) method, the Cambridge sequential total energy program package (CASTEP) is used to simulate seven kinds of highly symmetric adsorption structure models of termination with tetrahedral Fe (A termination) and termination with octahedral Fe (B termination) on FeO (0 0 1) surface. The adsorption energies and stable adsorption conformations are calculated. The results show that the most stable adsorption structures of the Fe/FeO (0 0 1) configurations are Fe above Fe-O bond of B layer termination (FeO(001) A-b). During the adsorption, the Fe-Fe, Fe-O bond length, and Fe-Fe-O bond angle of (0 0 1) surface change, and the atomic positions parallel and perpendicular to (0 0 1) surface change correspondingly. The change happened to the surface layer is the most drastic one. The calculation of charge population, the density of states (DOS), and electron local function of Fe/FeO (0 0 1) optimal adsorption configuration show that there is electron transfer between Fe and FeO (0 0 1), and the adsorption type is chemisorption. Among them, Fe (Fe)-Fe (FeO) forms a metal bond, and Fe (Fe)-O (FeO) forms the ionic bond. The results illustrate the interaction between free Fe and FeO is the reason of the nucleation and agglomeration of FeO scale and it provides the foundation for the further research on FeO scale deposition.
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http://dx.doi.org/10.1007/s00894-021-04802-4DOI Listing
May 2021

Lateral ventricular medulloepithelioma in children: a case report.

Transl Pediatr 2021 Apr;10(4):1020-1025

Department of Neurosurgery, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, China.

Medulloepithelioma is an extremely rare highly malignant and rapidly growing tumor that occurs in the central nervous system. There are few reports of medulloepithelioma located in the ventricle. Medulloepithelioma is common in young children and adolescence. Herein, we described an unusual case of vomiting in a 4-year-old male patient with medulloepithelioma, presenting with enlarging head circumference. Because of computed tomography (CT) scan of the head showed signs of brain tumors and hydrocephalus, and enhanced magnetic resonance imaging (MRI) sequence showed increased heterogeneity and honeycomb-like changes on the mass after the administration of a contrast agent, the patient was first diagnosed as choroid plexus papilloma. After undergoing a surgical craniotomy, the patient was diagnosed as medulloepithelioma through pathological examination. We hope that this work will provide more understanding and knowledge of intracranial medulloepithelioma. For medulloepithelioma that occurs in the central nervous system, radiological examination is not sufficient to make a definite diagnosis of the tumor. Pathological examination can confirm the diagnosis of medulloepithelioma and distinguish it from other central system tumors. Surgical resection is a safe and effective method that can prolong the life of patients. However, the prognosis of medulloepithelioma is still poor, and further research is needed to improve the diagnosis and treatment of this rare disease.
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http://dx.doi.org/10.21037/tp-20-257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107848PMC
April 2021

Bronchial glomus tumor with calcification: A case report.

World J Clin Cases 2021 May;9(14):3320-3326

Department of Pulmonary and Critical Care Medicine, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian 116033, Liaoning Province, China.

Background: Glomus tumors (GTs), defined by modified smooth cells and normal glomus body cells, usually present with a small mass occurring in the soft tissue or dermis of an extremity, especially in the subungual region. However, other unusual sites, such as the respiratory tract, have also been reported. They are usually sporadic. Their imaging findings are usually nonspecific and likely to appear as a well-delineated round mass that usually lacks calcification. To our knowledge, we report the first case of bronchial GTs with calcification, reminding clinicians and radiologists that GT is one of the differential diagnoses when a calcified nodular mass is found.

Case Summary: We report a case of a 33-yr-old Chinese man with cough and sputum for 11 d and hemoptysis for 5 d. Chest computed tomography revealed a calcified nodular lesion on the compressed posterior wall of the lower left main bronchus and bronchiectasis in the lower lobe of the left lung. To confirm the characteristics of calcified nodules, we performed fiberoptic bronchoscopy. The tumor tissue from the biopsy of bronchial mucosal lesions established the diagnosis of GT. Because the patient had no life-threatening symptoms, he was not treated with surgery. Clinical follow-up for 25 mo showed that the patient survived well without any discomfort.

Conclusion: Bronchial GTs are usually not accompanied by calcification on computed tomography scans. To our knowledge, we report the first calcified bronchial GT. We recommend that clinicians consider GT as a possible differential diagnosis when a calcified mass of the bronchi is found.
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http://dx.doi.org/10.12998/wjcc.v9.i14.3320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107899PMC
May 2021

A multi-predictor model to predict risk of scleroderma renal crisis in systemic sclerosis: a multicentre, retrospective, cohort study.

Clin Exp Rheumatol 2021 May 14. Epub 2021 May 14.

Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, China.

Objectives: Scleroderma renal crisis (SRC) is a life-threatening syndrome. The early identification of patients at risk is essential for timely treatment to improve the outcome. Therefore, it is of great interest to provide a personalised tool to predict risk of SRC in systemic sclerosis (SSc).

Methods: We tried to set up a SRC prediction model based on the PKUPH-SSc cohort of 302 SSc patients. The least absolute shrinkage and selection operator (Lasso) regression was used to optimise disease features. Multivariable logistic regression analysis was applied to build a SRC prediction model incorporating the features of SSc selected in the Lasso regression. Then, a multi-predictor nomogram combining clinical characteristics was constructed and evaluated by discrimination and calibration, with further assessment by external validation in a validation cohort composed of 400 consecutive SSc patients from other 4 tertiary hospitals.

Results: A multi-predictor nomogram for evaluating the risk of SRC was successfully developed. In the nomogram, four easily available predictors were contained, including disease duration <2 years, cardiac involvement, anaemia and corticosteroid >15mg/d exposure. The nomogram displayed good discrimination with an area under the curve (AUC) of 0.843 (95% CI: 0.797-0.882) and good calibration. High AUC value of 0.854 (95% CI: 0.690-1.000) could still be achieved in the external validation. The model is now available online for research use.

Conclusions: The multi-predictor nomogram for SRC could be reliably and conveniently used to predict the individual risk of SRC in SSc patients, and be a step towards more personalised medicine.
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May 2021

The requirement of cellularity for abiogenesis.

Comput Struct Biotechnol J 2021 17;19:2202-2212. Epub 2021 Apr 17.

Laboratory of Biology and Information Science, Biomedical Synthetic Biology Research Center, School of Life Sciences, East China Normal University, Shanghai 200062, PR China.

The history of modern biochemistry started with the cellular theory of life. By putting aside the holistic protoplasmic theory, scientists of the XX century were able to advance the functional classification of cellular components significantly. The cell became the unit of the living. Current theories on the abiogenesis of life must account for a moment in evolution (chemical or biological) when this was not the case. Investigating the role of compartments and membranes along chemical and biotic evolution can lead a more generalised idea of living organisms that is fundamental to advance our efforts in astrobiology, origin of life and artificial life studies. Furthermore, it may provide insights in unexplained evolutionary features such as the lipid divide between Archaea and Eubacteria. By surveying our current understanding of the involvement of compartments in abiogenesis and evolution, the idea of cells as atomistic units of a general theory of biology will be discussed. The aim is not to undermine the validity of the cellular theory of life, but rather to elucidate possible biases with regards to cellularity and the origin of life. An open discussion in these regards could show the inherent limitations of non-cellular compartmentalization that may lead to the necessity of cellular structures to support complex life.
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http://dx.doi.org/10.1016/j.csbj.2021.04.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099592PMC
April 2021

Differential fluorescence microscopy by using a dynamic cylindrical-vector field.

Opt Lett 2021 May;46(10):2332-2335

Fluorescence emission difference (FED) microscopy, as an emerging super-resolution imaging modality, uses double-exposure and subtraction between double-exposed fluorescence images to achieve high spatial resolution beyond the diffraction limit. Here we report on a new FED imaging approach with a single-exposure scheme based on dynamic cylindrical-vector fields, where the fluorescence excitation beam can be switched between radial and azimuthal polarization states at a designated high radio frequency. Lateral spatial resolution of ${\sim} \lambda/4$ is achieved. Being able to integrate with lock-in amplifier detection, the proposed method will find promising applications for high-speed fluorescence imaging with improved signal-to-noise ratio.
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http://dx.doi.org/10.1364/OL.425033DOI Listing
May 2021

aFGF Targeted Mediated by Novel Nanoparticles-Microbubble Complex Combined With Ultrasound-Targeted Microbubble Destruction attenuates Doxorubicin-Induced Heart Failure via Anti-Apoptosis and Promoting Cardiac Angiogenesis.

Front Pharmacol 2021 27;12:607785. Epub 2021 Apr 27.

Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, China.

The purpose of this study was to evaluate the protective effect of acidic fibroblast growth factor targeted mediated by novel nanoparticles-cationic lipid microbubbles complex (aFGF-NP + CPMBs) combined with ultrasound targeted microbubble destruction (UTMD)on doxorubicin-induced heart failure (HF)and its mechanism. Heart failure rats induced by intraperitoneal injection with doxorubicin (DOX) to achieve cummulative dose of 15mg/kg for continuous 6 weeks showed left ventricular dysfunction, seriously oxidative stress, cardiomyocyte apoptosis, and decrease of myocardial vascular density. In contrast, aFGF-NP + CPMBs combined with UTMD therapy (3ug/kg, caudal vein injection, twice a week, 6weeks)prominently ameliorated left ventricular dysfunction by increased ejection fraction (EF) and fractional shortening (FS), decreased brain natriuretic peptide (BNP); strengthened the ability of antioxidant stress confirmed by increasing the activity of SOD and reducing the production of MDA; exerted the effect of anti-cardiomyocyte apoptosis and promotion angiogenesis by inhibited Bax expression and increased Bcl-2 expression and platelet endothelial cell adhesion molecule (CD31) expression. Taken together, the research suggested that aFGF targeted mediated by novel nanoparticles-cationic lipid microbubbles complex combined with UTMD should be a promising targeted treatment for heart failure.
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http://dx.doi.org/10.3389/fphar.2021.607785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111001PMC
April 2021

Renal artery embolization in the treatment of urinary fistula after renal duplication: A case report and review of literature.

World J Clin Cases 2021 May;9(13):3177-3184

Department of Interventional Radiology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210029, Jiangsu Province, China.

Background: Duplicate renal malformation is a congenital disease of the urinary system, with an incidence rate of 0.8%. Surgical treatment is suitable for symptomatic patients. Urinary fistula is one of the complications of heminephrectomy. Long-term urinary fistula has a great impact on patients' lives.

Case Summary: This article mainly reports on a 47-year-old man with duplication of kidney deformity, long urinary fistula after partial nephrectomy, and no improvement after conservative treatment. We have achieved positive results in the arterial embolization treatment of the residual renal artery, indicating that selective arterial embolization is a good way to treat urinary fistula after partial nephrectomy. It is worth noting that this patient violated the Weigert-Meyer law, which also gave us more consideration.

Conclusion: Renal artery embolization may be a simple and safe method to treat urinary fistula inefficacy with conservative treatment.
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http://dx.doi.org/10.12998/wjcc.v9.i13.3177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080745PMC
May 2021

Patient-reported outcomes from a randomized, double-blind, placebo controlled, phase III study of baricitinib placebo in patients with moderately to severely active rheumatoid arthritis and an inadequate response to methotrexate therapy: results from the RA-BALANCE study.

Ther Adv Musculoskelet Dis 2021 20;13:1759720X211006964. Epub 2021 Apr 20.

Department of Rheumatology and Immunity, Center of Clinical Immunology, Peking University People's Hospital, Xicheng District, Beijing, P.R. China.

Introduction: To assess the effect of baricitinib on patient-reported outcomes (PROs) in patients with moderately to severely active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX).

Methods: This was a 52-week, randomized, double-blind, placebo controlled, phase III study in patients with RA who had an inadequate response to MTX. Patients ( = 290) receiving stable background MTX were randomly assigned (1:1) to receive placebo or baricitinib 4 mg once daily with a primary endpoint at week 12. PROs assessed included Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient's Global Assessment of Disease Activity, patient's assessment of pain, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), European Quality of Life-5 Dimensions-5 Level index scores and visual analogue scale, and measures collected in electronic patient daily diaries: duration of morning joint stiffness, Worst Tiredness, and Worst Joint Pain. Treatment comparisons were made with logistic regression and analysis of covariance models for categorical and continuous variables, respectively.

Results: Statistically significant ( ⩽ 0.05) improvements in all PROs were observed in the baricitinib 4 mg group compared to placebo as early as week 1 to week 4; and were sustained to week 24. These improvements were maintained until week 52 for the baricitinib group. A significantly larger proportion of patients met or exceeded the minimum clinically important difference for HAQ-DI (⩾0.22) and FACIT-F (3.56) profiles in the baricitinib group.

Conclusion: Baricitinib provided significant improvements in PROs compared to placebo to 52 weeks of treatment in patients with RA who had an inadequate response to MTX.Clinicaltrials.gov identifier: https://clinicaltrials.gov/ct2/show/NCT02265705; NCT02265705; RA-BALANCE. Registered 13 October 2014.
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http://dx.doi.org/10.1177/1759720X211006964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064513PMC
April 2021

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism and obstructive sleep apnoea in a Chinese population: A meta-analysis.

J Renin Angiotensin Aldosterone Syst 2020 Apr-Jun;21(2):1470320320934716. Epub 2020 Jun 17.

Department of Respiratory and Critical Care Medicine, ShenZhen Hospital of Southern Medical University, PR China.

Introduction: Many studies have investigated the association between angiotensin-converting enzyme () gene insertion/deletion (I/D) polymorphism and susceptibility to obstructive sleep apnoea (OSA). However, few have confirmed the relationship between ACE and OSA in the Chinese population. We performed a meta-analysis of studies relating the I/D polymorphism to the risk of OSA in a Chinese population.

Methods: We evaluated eligible published studies from several databases for this meta-analysis. Subgroup analyses were performed for hypertension. Pooled odds ratios and 95% confidence intervals were calculated using a fixed- or random-effects model.

Results: Ten studies were identified to analyse the association between I/D polymorphism and OSA risk. No marked associations were found in any genetic model (>0.05). Subgroup analysis showed an association with hypertension (D vs. I, DD vs. II, ID vs. DD+II, DD+ID vs. II, ID vs. II; <0.05), which was confirmed by sensitivity analyses. No obvious publication bias was found using Egger's test (>0.05).

Conclusions: The I/D polymorphism was not associated with an increased risk of OSA in a Chinese population. However, within the hypertensive subgroup, we detected a significant association between the polymorphism and OSA. More case-control investigations are required.
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http://dx.doi.org/10.1177/1470320320934716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301659PMC
June 2020

Clinical value for the detection of fetal chromosomal deletions/duplications by noninvasive prenatal testing in clinical practice.

Mol Genet Genomic Med 2021 May 5:e1687. Epub 2021 May 5.

Center for Genetic Medicine, Xuzhou Maternity and Child Health Care Hospital Affiliated to Xuzhou Medical University, Xuzhou, China.

Objective: This study was to report the experiences on the clinical value of noninvasive prenatal testing (NIPT) for the screening of fetal chromosomal deletions/duplications.

Methods: We performed a retrospective analysis of a cohort of 20,439 pregnancies undergoing NIPT from March 2017 to September 2020 at a single center. Patients with positive NIPT results for fetal chromosomal deletions or duplications had options of invasive diagnostic testing or no further testing. The data were complied from all cases with positive NIPT results for chromosomal deletions/duplications. The positive predictive value (PPV) was calculated from tabulated data.

Results: In this cohort, positive NIPT results for fetal chromosomal deletions/duplications were found in 60 pregnant women. Of the positive samples, further invasive testing was performed in 39 cases, in which 9 cases were found to be true positive. The overall PPV for chromosomal deletions/duplications was 23.1%. In addition, fetal structural anomaly was found by ultrasound examination in three cases, in which the chromosomal deletions/duplications of three cases were not verified. Moreover, an unexpected pathogenic 8p23.3 deletion was identified by invasive testing in 1 fetus with a false positive NIPT screen for 3q27.3q29 duplication.

Conclusions: In summary, positive NIPT results of chromosomal deletions/duplications were not uncommon in clinical practice, whereas the PPV for the testing was low. Hence, potential risks and high percentage of false positives for these abnormal NIPT results might be informed to pregnant women before the choice made of invasive testing.
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http://dx.doi.org/10.1002/mgg3.1687DOI Listing
May 2021

FGF21 Normalizes Plasma Glucose in Mouse Models of Type 1 Diabetes and Insulin Receptor Dysfunction.

Endocrinology 2021 May 5. Epub 2021 May 5.

Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.

Fibroblast growth factor 21 (FGF21) is a member of the fibroblast growth factor (FGF) family of proteins. The biological activity of FGF21 was first shown to induce insulin independent glucose uptake in adipocytes through the GLUT1 transporter. Subsequently, it was shown to have effects on the liver to increase fatty acid oxidation. FGF21 treatment provides beneficial metabolic effects in both animal models and patients with obesity, type 2 diabetes mellitus (T2D) and/or fatty liver disease. In this paper, we revisited the original finding and found that insulin independent glucose uptake in adipocytes is preserved in the presence of an insulin receptor antagonist. Using a 40 kDa PEGylated (PEG) and half-life extended form of FGF21 (FGF21-PEG), we extended these in vitro results to two different mouse models of diabetes. FGF21-PEG normalized plasma glucose in streptozotocin-treated mice, a model of type 1 diabetes (T1D), without restoring pancreatic β-cell function. FGF21-PEG also normalized plasma glucose levels and improved glucose tolerance in mice chronically treated with an insulin competitive insulin receptor antagonist, a model of autoimmune/Type-B insulin resistance. These data extend the pharmacological potential of FGF21 beyond the settings of T2D, fatty liver and obesity.
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http://dx.doi.org/10.1210/endocr/bqab092DOI Listing
May 2021

Clinical characteristics of axial spondyloarthritis patients in China: results from ChinaSpA, the Chinese Spondyloarthritis Registry.

Clin Exp Rheumatol 2021 Apr 23. Epub 2021 Apr 23.

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education; National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China.

Objectives: The objective of this study is to describe the clinical features of patients with axial spondyloarthritis (axial SpA) in the ChinaSpA registry.

Methods: Patients with clinical diagnosis of ankylosing spondylitis (AS) or axial SpA were enrolled into the registry. Patients with a complete set of pelvis radiograph, pelvis MRI and HLA-B27 (Complete Set group, CS group) were further categorised based on classification criteria into AS, radiographic axial SpA (r-axSpA) and non-radiographic axial SpA (nr-axSpA). Early axial SpA was defined as symptom duration of less than three years. Descriptive statistics were used to describe clinical characteristics of enrolled patients. ANOVA analyses were used to compare patients in different groups.

Results: A total of 5270 patients were enrolled in the study, and 3223 patients had complete sets of pelvis radiographs, MRIs and HLA-B27 status. Among them, more than 80% patients met both the ASAS criteria for r-axSpA and the modified New York criteria for AS. Among those with early axial SpA, 92% of patients had sacroiliitis on pelvis radiograph, 3.8% had sacroiliitis only on pelvis MRI, and 3.8% were in the clinical arm without any sacroiliitis on imaging studies. Patients in nr-axSpA clinical arm had less diagnosis delay, lower inflammatory markers and ASDAS, compared topatients in the r-axSpA, nr-axSpA MRI arm.

Conclusions: In the ChinaSpA registry, patients in nr-axSpA clinical arm had the shortest diagnostic delay, lower inflammatory markers and ASDAS, but no difference in extra-articular manifestation, compared to patients in the r-axSpA and nr-axSpA MRI arm.
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April 2021

Identification of a MicroRNA Signature Associated With Lymph Node Metastasis in Endometrial Endometrioid Cancer.

Front Genet 2021 15;12:650102. Epub 2021 Apr 15.

Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: Lymph node metastasis (LNM) is an important prognostic factor in endometrial cancer. Anomalous microRNAs (miRNAs) are associated with cell functions and are becoming a powerful tool to characterize malignant transformation and metastasis. The aim of this study was to construct a miRNA signature to predict LNM in endometrial endometrioid carcinoma (EEC).

Method: Candidate target miRNAs related to LNM in EEC were screened by three methods including differentially expressed miRNAs (DEmiRs), weighted gene co-expression network analysis (WGCNA), and decision tree algorithms. Samples were randomly divided into the training and validation cohorts. A miRNA signature was built using a logistic regression model and was evaluated by the area under the curve (AUC) of receiver operating characteristic curve (ROC) and decision curve analysis (DCA). We also conducted pathway enrichment analysis and miRNA-gene regulatory network to look for potential genes and pathways engaged in LNM progression. Survival analysis was performed, and the miRNAs were tested whether they expressed differently in another independent GEO database.

Result: Thirty-one candidate miRNAs were screened and a final 15-miRNA signature was constructed by logistic regression. The model showed good calibration in the training and validation cohorts, with AUC of 0.824 (95% CI, 0.739-0.912) and 0.821 (95% CI, 0.691-0.925), respectively. The DCA demonstrated the miRNA signature was clinically useful. Hub miRNAs in signature seemed to contribute to EEC progression mitotic cell cycle, cellular protein modification process, and molecular function. MiR-34c was statistically significant in survival that a higher expression of miR-34c indicated a higher survival time. MiR-34c-3p, miR-34c-5p, and miR-34b-5p were expressed differentially in GSE75968.

Conclusion: The miRNA signature could work as a noninvasive method to detect LNM in EEC with a high prediction accuracy. In addition, miR-34c cluster may be a key biomarker referring LNM in endometrial cancer.
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http://dx.doi.org/10.3389/fgene.2021.650102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082502PMC
April 2021

Wearable Glucose Monitoring and Implantable Drug Delivery Systems for Diabetes Management.

Adv Healthc Mater 2021 Apr 30:e2100194. Epub 2021 Apr 30.

Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, 47907, USA.

The global cost of diabetes care exceeds $1 trillion each year with more than $327 billion being spent in the United States alone. Despite some of the advances in diabetes care including continuous glucose monitoring systems and insulin pumps, the technology associated with managing diabetes has largely remained unchanged over the past several decades. With the rise of wearable electronics and novel functional materials, the field is well-poised for the next generation of closed-loop diabetes care. Wearable glucose sensors implanted within diverse platforms including skin or on-tooth tattoos, skin-mounted patches, eyeglasses, contact lenses, fabrics, mouthguards, and pacifiers have enabled noninvasive, unobtrusive, and real-time analysis of glucose excursions in ambulatory care settings. These wearable glucose sensors can be integrated with implantable drug delivery systems, including an insulin pump, glucose responsive insulin release implant, and islets transplantation, to form self-regulating closed-loop systems. This review article encompasses the emerging trends and latest innovations of wearable glucose monitoring and implantable insulin delivery technologies for diabetes management with a focus on their advanced materials and construction. Perspectives on the current unmet challenges of these strategies are also discussed to motivate future technological development toward improved patient care in diabetes management.
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http://dx.doi.org/10.1002/adhm.202100194DOI Listing
April 2021