Publications by authors named "Cheng Wang"

2,796 Publications

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Effective high-throughput screening of two-dimensional layered materials for potential lithium-ion battery anodes.

Dalton Trans 2022 Jun 28. Epub 2022 Jun 28.

College of Science, Hohai University, Nanjing, Jiangsu 210098, China.

Lithium-ion batteries (LIBs) are considered the promising next-generation advanced energy storage devices. It is very important to quickly screen out ideal anode materials for LIBs with excellent performance. In this work, an effective procedure is designed for the high-throughput screening of the three kinds of LIB anode materials from 131 613 inorganic compounds in the Materials Project database. The high throughput screen procedure was not only reliable but was also easily realized. Three ideal anode materials were obtained by considering remarkable thermodynamic stability, Li capacity larger than 372 mA h g, band gap smaller than 1.0 eV, and two-dimensional constraint. Furthermore, open-circuit voltage, volume expansion ratio, and the diffusion energy barrier were calculated by the DFT-D corrected density functional method. We believe that our high throughput screen procedure can effectively and accurately search for other kinds of anode materials, which can strongly support the theoretical basis for experimental research.
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http://dx.doi.org/10.1039/d2dt01769eDOI Listing
June 2022

Human papillomavirus targets the YAP1-LATS2 feedback loop to drive cervical cancer development.

Oncogene 2022 Jun 27. Epub 2022 Jun 27.

Vincent Center for Reproductive Biology, Vincent Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.

Human papillomavirus (HPV) infection is very common in sexually active women, but cervical cancer only develops in a small fraction of HPV-infected women, suggesting that unknown intrinsic factors associated with the unique genetic/genomic background of the high-risk population play a critical role in cervical carcinogenesis. Although our previous studies have identified the hyperactivated YAP1 oncogene as a critical contributor to cervical cancer, the molecular mechanism by which YAP1 drives cervical cancer is unknown. In the present study, we found that although the hyperactivated YAP1 caused a malignant transformation of immortalized cervical epithelial cells, it induced cellular senescence in cultures of primary human cervical epithelial cells (HCvECs). However, the hyperactivated YAP1 induced malignant transformation of HCvECs in the presence of high-risk HPV E6/E7 proteins, suggesting that the hyperactivated YAP1 synergizes with HPV to initiate cervical cancer development. Our mechanistic studies demonstrate that YAP1, via up-regulating LATS2, formed a YAP1-LATS2 negative feedback loop in cervical epithelial cells to maintain homeostasis of cervical tissue. Intriguingly, we found that high-risk HPV targets LATS2 to disrupt the feedback loop leading to the malignant transformation of cervical epithelial cells. Finally, we report that mitomycin C, an FDA-approved drug that could upregulate LATS2 and drive cellular senescence in vitro and in vivo, induced a regression of cervical cancer in a pre-clinial animal model. Thus, high-risk HPV targeting the YAP1-LATS2 feedback loop represents a new mechanism of cervical cancer development.
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http://dx.doi.org/10.1038/s41388-022-02390-yDOI Listing
June 2022

Inhibition of lipid kinase PIKfyve reveals a role for phosphatase Inpp4b in the regulation of PI(3)P-mediated lysosome dynamics through VPS34 activity.

J Biol Chem 2022 Jun 24:102187. Epub 2022 Jun 24.

Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Electronic address:

Lysosome membranes contain diverse phosphoinositide (PtdIns) lipids that coordinate lysosome function and dynamics. The PtdIns repertoire on lysosomes is tightly regulated by the actions of diverse PtdIns kinases and phosphatases; however, specific roles for PtdIns in lysosomal functions and dynamics are currently unclear and require further investigation. It was previously shown that PIKfyve, a lipid kinase that synthesizes PtdIns(3,5)P from PtdIns(3)P, controls lysosome "fusion-fission" cycle dynamics, autophagosome turnover, and endocytic cargo delivery. Furthermore, INPP4B, a PtdIns 4-phosphatase that hydrolyzes PtdIns(3,4)P to form PtdIns(3)P, is emerging as a cancer-associated protein with roles in lysosomal biogenesis and other lysosomal functions. Here, we investigated the consequences of disrupting PIKfyve function in Inpp4b-deficient mouse embryonic fibroblasts. Through confocal fluorescence imaging, we observed the formation of massively enlarged lysosomes, accompanied by exacerbated reduction of endocytic trafficking, disrupted lysosome fusion-fission dynamics, and inhibition of autophagy. Finally, HPLC scintillation quantification of H-myo-inositol labelled phosphoinositides and phosphoinositide immunofluorescence staining, we observed that lysosomal PtdIns(3)P levels were significantly elevated in Inpp4b-deficient cells due to the hyperactivation of phosphatidylinositol 3-kinase catalytic subunit VPS34 enzymatic activity. In conclusion, our study identifies a novel signaling axis that maintains normal lysosomal homeostasis and dynamics, which includes the catalytic functions of Inpp4b, PIKfyve, and VPS34.
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http://dx.doi.org/10.1016/j.jbc.2022.102187DOI Listing
June 2022

Risk Factors and Prognostic Follow-Up of Vasovagal Syncope Children With Seizure-Like Activities During Head-Up Tilt Test Induced-Syncope.

Front Cardiovasc Med 2022 10;9:916542. Epub 2022 Jun 10.

Department of Pediatric Cardiovasology, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, China.

Objectives: To analyze the risk factors associated with seizure-like activities during head up tilt test (HUTT)-induced syncope in children with vasovagal syncope (VVS) and assess the prognosis of these patients.

Methods: This is a retrospective study. VVS children with or without seizure-like activities during HUTT-induced syncope were included in convulsive or non-convulsive group. The clinical characteristics, hemodynamic parameters during HUTT-induced syncope and follow-up data were reviewed from the HUTT case report form and analyzed.

Results: 68 cases (25 males, mean age 11.86 ± 3.35 years) were enrolled in convulsive group and 65 cases in non-convulsive group (24 males, mean age 11.64 ± 2.11 years). There were statistical differences in history duration, response type, and asystole between the two groups (all < 0.05). Fully adjusted logistic regression showed that the risk of seizure-like activities was increased by 37.18 folds for patients with asystole compared with those without asystole ( = 0.005), by 308.25 and 6.08 folds for patients with cardioinhibitory type or mixed type compared with vasoinhibitory type ( < 0.01). No significant difference was exhibited in negative HUTT conversion rate and the proportion of re-syncope patients between the two groups at follow-up (both > 0.05). None of these convulsive patients underwent pacemaker implantation during follow-up.

Conclusions: Asystole and response type were independent risk factors associated with seizure-like activities. Patients with asystole and mixed or cardioinhibitory responses to HUTT should be closely concerned. However, VVS children with seizure-like activities did not have a poor prognosis at follow-up.
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http://dx.doi.org/10.3389/fcvm.2022.916542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226399PMC
June 2022

EEG-Based Epileptic Seizure Detection via Machine/Deep Learning Approaches: A Systematic Review.

Comput Intell Neurosci 2022 17;2022:6486570. Epub 2022 Jun 17.

CAS Key Laboratory of Human-Machine Intelligence-Synergy Systems, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

Epileptic seizure is one of the most chronic neurological diseases that instantaneously disrupts the lifestyle of affected individuals. Toward developing novel and efficient technology for epileptic seizure management, recent diagnostic approaches have focused on developing machine/deep learning model (ML/DL)-based electroencephalogram (EEG) methods. Importantly, EEG's noninvasiveness and ability to offer repeated patterns of epileptic-related electrophysiological information have motivated the development of varied ML/DL algorithms for epileptic seizure diagnosis in the recent years. However, EEG's low amplitude and nonstationary characteristics make it difficult for existing ML/DL models to achieve a consistent and satisfactory diagnosis outcome, especially in clinical settings, where environmental factors could hardly be avoided. Though several recent works have explored the use of EEG-based ML/DL methods and statistical feature for seizure diagnosis, it is unclear what the advantages and limitations of these works are, which might preclude the advancement of research and development in the field of epileptic seizure diagnosis and appropriate criteria for selecting ML/DL models and statistical feature extraction methods for EEG-based epileptic seizure diagnosis. Therefore, this paper attempts to bridge this research gap by conducting an extensive systematic review on the recent developments of EEG-based ML/DL technologies for epileptic seizure diagnosis. In the review, current development in seizure diagnosis, various statistical feature extraction methods, ML/DL models, their performances, limitations, and core challenges as applied in EEG-based epileptic seizure diagnosis were meticulously reviewed and compared. In addition, proper criteria for selecting appropriate and efficient feature extraction techniques and ML/DL models for epileptic seizure diagnosis were also discussed. Findings from this study will aid researchers in deciding the most efficient ML/DL models with optimal feature extraction methods to improve the performance of EEG-based epileptic seizure detection.
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http://dx.doi.org/10.1155/2022/6486570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232335PMC
June 2022

Screening New Blood Indicators for Non-alcoholic Fatty Liver Disease (NAFLD) Diagnosis of Chinese Based on Machine Learning.

Front Med (Lausanne) 2022 9;9:771219. Epub 2022 Jun 9.

Department of General Practice, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, China.

Background: The prevalence of NAFLD is increasing annually. The early diagnosis and control are crucial for the disease. Currently, metabolic indicators are always used clinically as an auxiliary diagnosis of NAFLD. However, the prevalence of NAFLD is not only increased in obese/metabolic-disordered populations. NAFLD patients with thin body are also increasing. Only using metabolic indicators to assist in the diagnosis of NAFLD may have some deficiencies. Continue to develop more clinical auxiliary diagnostic indicators is pressing.

Methods: Machine learning methods are applied to capture risk factors for NAFLD in 365 adults from Zhejiang Province. Predictive models are constructed for NAFLD using fibrinolytic indicators and metabolic indicators as predictors respectively. Then the predictive effects are compared; ELISA kits were used to detect the blood indicators of non-NAFLD and NAFLD patients and compare the differences.

Results: The prediction accuracy for NAFLD based on fibrinolytic indicators [Tissue Plasminogen Activator (TPA), Plasminogen Activator Inhibitor-1 (PAI-1)] is higher than that based on metabolic indicators. TPA and PAI-1 are more suitable than metabolic indicators to be selected to predict NAFLD.

Conclusions: The fibrinolytic indicators have a stronger association with NAFLD than metabolic indicators. We should attach more importance to TPA and PAI-1, in addition to TC, HDL-C, LDL-C, and ALT/AST, when conducting blood tests to assess NAFLD.
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http://dx.doi.org/10.3389/fmed.2022.771219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218755PMC
June 2022

A probe-free electrochemical immunosensor for methyl jasmonate based on a Cu-MOF-carboxylated graphene oxide platform.

RSC Adv 2022 Jun 6;12(26):16688-16695. Epub 2022 Jun 6.

Intelligent Equipment Research Center, Beijing Academy of Agriculture and Forestry Sciences Beijing 100097 China

Methyl jasmonate (MeJA) is an important phytohormone which can regulate plant growth and stress tolerance. It is very necessary to develop sensitive and accurate detection methods for MeJA. In this work, a probe-free electrochemical immunosensor for MeJA detection was developed based on a Cu-MOF-carboxylated graphene oxide (COOH-GO) platform. The Cu in the Cu-MOFs was used to provide redox signals, which avoids the application of an external redox probe in the electrolyte solutions as conventional immunosensors. COOH-GO was used to improve the structural stability and provide more sites for binding MeJA antibodies. The linear range of the MeJA immunosensor is from 10 pM to 100 μM, which can cover the whole concentration range of MeJA in most plants. And its detection limit is very low (0.35 pM), and it can detect very low concentrations of MeJA. This immunosensor is simple, low cost, and does not need redox probe solutions for measurements. It shows remarkable potential for on-site application in precision agriculture.
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http://dx.doi.org/10.1039/d1ra07683cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169702PMC
June 2022

Single-cell RNA-sequencing of zebrafish hair cells reveals novel genes potentially involved in hearing loss.

Cell Mol Life Sci 2022 Jun 26;79(7):385. Epub 2022 Jun 26.

School of Life Sciences, Nantong Laboratory of Development and Diseases, Nantong University, Nantong, 226019, China.

Hair cells play key roles in hearing and balance, and hair cell loss would result in hearing loss or vestibular dysfunction. Cellular and molecular research in hair cell biology provides us a better understanding of hearing and deafness. Zebrafish, owing to their hair cell-enriched organs, have been widely applied in hair cell-related research worldwide. Similar to mammals, zebrafish have inner ear hair cells. In addition, they also have lateral line neuromast hair cells. These different types of hair cells vary in morphology and function. However, systematic analysis of their molecular characteristics remains lacking. In this study, we analyzed the GFP+ cells isolated from Tg(Brn3c:mGFP) larvae with GFP expression in all hair cells using single-cell RNA-sequencing (scRNA-seq). Three subtypes of hair cells, namely macula hair cell (MHC), crista hair cell (CHC), and neuromast hair cell (NHC), were characterized and validated by whole-mount in situ hybridization analysis of marker genes. The hair cell scRNA-seq data revealed hair cell-specific genes, including hearing loss genes that have been identified in humans and novel genes potentially involved in hair cell formation and function. Two novel genes were discovered to specifically function in NHCs and MHCs, corresponding to their specific expression in NHCs and MHCs. This study allows us to understand the specific genes in hair cell subpopulations of zebrafish, which will shed light on the genetics of both human vestibular and cochlear hair cell function.
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http://dx.doi.org/10.1007/s00018-022-04410-2DOI Listing
June 2022

Clinical Observation and Value Analysis of Endovascular Interventional Therapy for Intracranial Venous Sinus Thrombosis.

Biomed Res Int 2022 14;2022:4931210. Epub 2022 Jun 14.

Department of Neurosurgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China.

The main aim of this study was to investigate the therapeutic effect of endovascular interventional therapy on cerebral venous sinus thrombosis (CVST). 137 patients with CVST were included, 92 patients were treated with interventional therapy, and 45 patients were treated with conventional anticoagulant therapy. Through endovascular therapy (EVT) combined with therapy, the patients were treated with EVT in combination with conventional anticoagulant therapy, and the prognosis of the two groups of patients was evaluated. The results showed that 26 patients were complicated with female-specific infections in the combined EVT group, and 7 patients had female-specific infections in the simple anticoagulant therapy (LMWH) group. In terms of central nervous system infections, the EVT group was significantly lower than the LMWH group, < 0.001, and the difference was statistically significant. There were 2 cases of EVT involving the inferior sagittal sinus and 12 cases of LMWH involving the inferior sagittal sinus, < 0.001, and the difference had statistical significance. Through the RANKIN scale (mRS) score, it was classified as complete recovery and good prognosis (dependent variable). The patients receiving EVT with good prognosis (96.7%) were more than those receiving simple anticoagulant therapy (84.4%), and 78.3% were completely recovered after EVT, and 77.5% were completely recovered after anticoagulant therapy. Therefore, it can be concluded that gender, malignant tumors, thrombosis, and sinuses are all risk factors affecting the prognosis of patients; both endovascular interventional therapy and anticoagulant therapy can significantly improve the prognosis of patients.
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http://dx.doi.org/10.1155/2022/4931210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213190PMC
June 2022

Exogenous Zeaxanthin Alleviates Low Temperature Combined with Low Light Induced Photosynthesis Inhibition and Oxidative Stress in Pepper ( L.) Plants.

Curr Issues Mol Biol 2022 May 25;44(6):2453-2471. Epub 2022 May 25.

College of Horticulture, Gansu Agricultural University, Lanzhou 730070, China.

Low temperature combined with low light (LL) affects crop production, especially the yield and quality of peppers, in northwest China during the winter and spring seasons. Zeaxanthin (Z) is a known lipid protectant and active oxygen scavenger. However, whether exogenous Z can mitigate LL-induced inhibition of photosynthesis and oxidative stress in peppers remains unclear. In this study, we investigated the effects of exogenous Z on photosynthesis and the antioxidant machinery of pepper seedlings subject to LL stress. The results showed that the growth and photosynthesis of pepper seedlings were significantly inhibited by LL stress. In addition, the antioxidant machinery was disturbed by the uneven production and elimination of reactive oxygen species (ROS), which resulted in damage to the pepper. For example, membrane lipid peroxidation increased ROS content, and so on. However, exogenous application of Z before LL stress significantly increased the plant height, stem diameter, net photosynthetic rate (Pn), and stomata, which were obviously closed at LL. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), mono de-hydroascorbate reductase (MDHAR), de-hydroascorbate reductase (DHAR), ascorbate peroxidase (APX), and ascorbate oxidase (AAO) improved significantly due to the increased expression of , , , , and . The ascorbic (AsA) and glutathione (GSH) contents and ascorbic/dehydroascorbate (AsA/DHA) and glutathione/oxidized glutathione (GSH/GSSG) ratios also increased significantly, resulting in the effective removal of hydrogen peroxide (HO) and superoxide anions (O) caused by LL stress. Thus, pre-treatment with Z significantly reduced ROS accumulation in pepper seedlings under LL stress by enhancing the activity of antioxidant enzymes and accumulation of components of the ascorbate-glutathione (AsA-GSH) cycle and upregulated key genes in the AsA-GSH cycle.
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http://dx.doi.org/10.3390/cimb44060168DOI Listing
May 2022

Gene amplification-driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A-YTHDF2-dependent in lung adenocarcinoma.

Cancer Commun (Lond) 2022 Jun 21. Epub 2022 Jun 21.

Department of Epidemiology, School of Public Health, Southeast University, Nanjing, Jiangsu, 210009, P. R. China.

Background: Epigenetic alterations have been shown to contribute immensely to human carcinogenesis. Dynamic and reversible N6-methyladenosine (m6A) RNA modification regulates gene expression and cell fate. However, the reasons for activation of KIAA1429 (also known as VIRMA, an RNA methyltransferase) and its underlying mechanism in lung adenocarcinoma (LUAD) remain largely unexplored. In this study, we aimed to clarify the oncogenic role of KIAA1429 in the tumorigenesis of LUAD.

Methods: Whole-genome sequencing and transcriptome sequencing of LUAD data were used to analyze the gene amplification of RNA methyltransferase. The in vitro and in vivo functions of KIAA1429 were investigated. Transcriptome sequencing, methylated RNA immunoprecipitation sequencing (MeRIP-seq), m6A dot blot assays and RNA immunoprecipitation (RIP) were performed to confirm the modified gene mediated by KIAA1429. RNA stability assays were used to detect the half-life of the target gene.

Results: Copy number amplification drove higher expression of KIAA1429 in LUAD, which was correlated with poor overall survival. Manipulating the expression of KIAA1429 could regulate the proliferation and metastasis of LUAD. Mechanistically, the target genes of KIAA1429-mediated m6A modification were confirmed by transcriptome sequencing and MeRIP-seq assays. We also revealed that KIAA1429 could regulate BTG2 expression in an m6A-dependent manner. Knockdown of KIAA1429 significantly decreased the m6A levels of BTG2 mRNA, leading to enhanced YTH m6A RNA binding protein 2 (YTHDF2, the m6A "reader")-dependent BTG2 mRNA stability and promoted the expression of BTG2; thus, participating in the tumorigenesis of LUAD.

Conclusions: Our data revealed the activation mechanism and important role of KIAA1429 in LUAD tumorigenesis, which may provide a novel view on the targeted molecular therapy of LUAD.
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http://dx.doi.org/10.1002/cac2.12325DOI Listing
June 2022

Impact of changes in protective behaviors and out-of-household activities by age on COVID-19 transmission and hospitalization in Chicago, Illinois.

Ann Epidemiol 2022 Jun 18. Epub 2022 Jun 18.

Argonne Distinguished Fellow and Group Leader, Argonne National Laboratory, Lemont, IL, Senior Scientist at Large, Consortium for Advanced Science and Engineering, University of Chicago, Chicago, IL, Senior Institute Fellow, Northwestern Argonne Institute for Science and Engineering, Evanston, IL.

Purpose: Even with an efficacious vaccine, protective behaviors (social distancing, masking) are essential for preventing COVID-19 transmission and could become even more important if current or future variants evade immunity from vaccines or prior infection.

Methods: We created an agent-based model representing the Chicago population and conducted experiments to determine the effects of varying adult out-of-household activities (OOHA), school reopening, and protective behaviors across age groups on COVID-19 transmission and hospitalizations.

Results: From September-November 2020, decreasing adult protective behaviors and increasing adult OOHA both substantially impacted COVID-19 outcomes; school reopening had relatively little impact when adult protective behaviors and OOHA were maintained. As of November 1, 2020, a 50% reduction in young adult (age 18-40) protective behaviors resulted in increased latent infection prevalence per 100,000 from 15.93 (IQR 6.18, 36.23) to 40.06 (IQR 14.65, 85.21)and 19.87 (IQR 6.83, 46.83) to 47.74 (IQR 18.89, 118.77) with 15% and 45% school reopening. Increasing adult (age ≥18) OOHA from 65% to 80% of pre-pandemic levels resulted in increased latent infection prevalence per 100,000 from 35.18 (IQR 13.59, 75.00) to 69.84 (IQR 33.27, 145.89) and 38.17 (IQR 15.84, 91.16) to 80.02 (IQR 30.91, 186.63) with 15% and 45% school reopening. Similar patterns were observed for hospitalizations.

Conclusions: In areas without widespread vaccination coverage, interventions to maintain adherence to protective behaviors, particularly among younger adults and in out-of-household settings, remain a priority for preventing COVID-19 transmission.
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http://dx.doi.org/10.1016/j.annepidem.2022.06.005DOI Listing
June 2022

Construction and Application of YOLOv3-Based Diatom Identification Model of Scanning Electron Microscope Images.

Fa Yi Xue Za Zhi 2022 Feb;38(1):46-52

Department of Forensic Medicine, Nanjing Medical University, Nanjing 211126, China.

Objectives: To construct a YOLOv3-based model for diatom identification in scanning electron microscope images, explore the application performance in practical cases and discuss the advantages of this model.

Methods: A total of 25 000 scanning electron microscopy images were collected at 1 500× as an initial image set, and input into the YOLOv3 network to train the identification model after experts' annotation and image processing. Diatom scanning electron microscopy images of lung, liver and kidney tissues taken from 8 drowning cases were identified by this model under the threshold of 0.4, 0.6 and 0.8 respectively, and were also identified by experts manually. The application performance of this model was evaluated through the recognition speed, recall rate and precision rate.

Results: The mean average precision of the model in the validation set and test set was 94.8% and 94.3%, respectively, and the average recall rate was 81.2% and 81.5%, respectively. The recognition speed of the model is more than 9 times faster than that of manual recognition. Under the threshold of 0.4, the mean recall rate and precision rate of diatoms in lung tissues were 89.6% and 87.8%, respectively. The overall recall rate in liver and kidney tissues was 100% and the precision rate was less than 5%. As the threshold increased, the recall rate in all tissues decreased and the precision rate increased. The 1 score of the model in lung tissues decreased with the increase of threshold, while the 1 score in liver and kidney tissues with the increase of threshold.

Conclusions: The YOLOv3-based diatom electron microscope images automatic identification model works at a rapid speed and shows high recall rates in all tissues and high precision rates in lung tissues under an appropriate threshold. The identification model greatly reduces the workload of manual recognition, and has a good application prospect.
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http://dx.doi.org/10.12116/j.issn.1004-5619.2021.410903DOI Listing
February 2022

The Relationship Between Unexplained Chest Pain in Children and Head-Up Tilt Test.

Front Pediatr 2022 2;10:901919. Epub 2022 Jun 2.

Department of Pediatric Cardiovasology, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, China.

Background: To explore the relationship between unexplained chest pain in children and head-up tilt test (HUTT).

Materials And Methods: A total of 825 children with the main symptom of unexplained chest pain were admitted to the Specialist Outpatient Clinic of Children's Cardiovascular Disease from October 2000 to November 2021 at The Second Xiangya Hospital, Central South University. Among them, 473 were male and 352 were female, with a mean age of 10.61 ± 2.21 years. The control group included 58 cases, comprising 35 males and 23 females, with a mean age of 10.26 ± 2.66 years. The detailed history, physical examinations, conventional 12-lead electrocardiogram, chest X-ray, echocardiography, myocardial enzymes, electroencephalogram, and blood series were all examined. Disorders of the chest wall, lung, heart, mediastinum, and esophageal reflux, as well as drug effects, were ruled out. All the children underwent HUTT. Demographic description, univariate analysis, and multivariate logistic regression analysis were used to explore the possible linear or non-linear relationships between the children's unexplained chest pain and HUTT.

Results: Among the 825 chest pain cases, 301 (36.48%) were HUTT positive and 524 (63.52%) were HUTT negative. HUTT-positive patients were older than HUTT-negative patients (11.04 ± 2.03 vs. 10.34 ± 2.31 years, < 0.001). The logistic regression results showed that each year of age increased the probability of being HUTT positive by 17.90% ( < 0.000), and females were 91.30% more likely to be HUTT positive than males ( < 0.000).

Conclusion: Clinically unexplained chest pain in children is mainly caused by unbalanced autonomic nervous function. HUTT can help clear the cause of unexplained chest pain.
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http://dx.doi.org/10.3389/fped.2022.901919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203148PMC
June 2022

MRI-Based Pancreatic Atrophy Is Associated With Malignancy or Invasive Carcinoma in Intraductal Papillary Mucinous Neoplasm.

Front Oncol 2022 3;12:894023. Epub 2022 Jun 3.

Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Background: Abrupt change in the caliber of the main pancreatic duct (MPD) with distal pancreatic atrophy (PA) was considered as one of worrisome features in the International Association of Pancreatology guideline and American College of Gastroenterology guideline for the management of intraductal papillary mucinous neoplasms (IPMNs). However, this feature was not included in other guidelines. Moreover, the association between PA alone and malignancy in IPMNs has not been fully evaluated. In the present study, we investigated the role of image-based PA in identifying malignant IPMNs or invasive carcinoma.

Methods: A total of 186 patients with IPMNs were included for analysis. The tumor size, location, MPD diameter, presence of a mural nodule (MN), and PA were evaluated using magnetic resonance imaging. Demographic information and serum carbohydrate antigen 19-9 and carcinoembryonic antigen (CEA) levels were also collected. IPMNs with high-grade dysplasia and associated invasive carcinoma were regarded as malignant IPMNs.

Results: PA was observed in 34 cases (18.3%). The occurrence of malignant IPMNs or invasive carcinoma in patients with PA were significantly higher than in those without PA (52.9% vs. 22.3%; 44.1% vs. 8.9%, all P < 0.01). Multivariate logistic regression analysis showed that PA was an independently associated factor for malignant IPMNs [odds ratio (OR) = 2.69, 95% confidence interval (CI): 1.07-6.78] or invasive carcinoma (OR = 7.78, 95%CI: 2.62-23.10) after modified with confounders. Subgroup analysis in MPD-involved IPMNs also indicated that PA was an independently associated factor for invasive carcinoma (OR = 9.72, 95%CI: 2.43-38.88). PA had a similar performance with MPD plus MN [the area under the curve (AUC) was both 0.71] in identifying malignancy. PA had a higher performance in identifying invasive carcinoma in MPD-involved IPMNs than MN (AUC = 0.71 vs. 0.65, P = 0.02).

Conclusion: Our data showed that imaging-based PA was associated with malignancy or invasive carcinoma regardless of abrupt change in the caliber of MPD in IPMNs. PA had an acceptable performance in identifying malignant IPMNs.
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http://dx.doi.org/10.3389/fonc.2022.894023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204001PMC
June 2022

Mechanism of pod shattering in the forage legume Medicago ruthenica.

Plant Physiol Biochem 2022 Jun 14;185:260-267. Epub 2022 Jun 14.

Grassland Research Institute, Chinese Academy of Agricultural Sciences, Hohhot, China; Key Laboratory of Herbage & Endemic Crop Biology, Ministry of Education, School of Life Sciences, Inner Mongolia University, Hohhot, China. Electronic address:

Pod shattering is a seed dispersal strategy and an important agronomical trait in domesticated crops. The relationship between pod shattering and pod morphology in the genus Medicago is well known; however, the detailed mechanism underlying pod dehiscence in Medicago ruthenica, a perennial legume used for forage production, is unknown. Here, the pod ventral sutures of shatter-resistant and shatter-susceptible M. ruthenica genotypes were examined at 8, 12, 16, and 20 d after flowering. The mechanism of pod shattering was analyzed through microscopic observations, polygalacturonase (PG) and cellulase (CE) activity analyses, and RNA-sequencing (RNA-Seq), and the results were verified via reverse transcriptase-quantitative polymerase chain reaction. Pod shattering at the ventral suture in M. ruthenica occurs via a combination of two mechanisms: degradation of the middle lamella at the abscission layers (ALs) and detachment of lignified cells on either side of the ALs triggered by physical forces. Increased PG and CE activities in the pod ventral suture are essential for AL cell-autolysis in the shatter-susceptible genotype. RNA-Seq revealed that 11 genes encoding PG and CE were highly expressed in the ventral sutures of the shatter-susceptible genotype. The expression levels of auxin biosynthesis-related genes decreased in the AL cells and they were negatively associated with pod dehiscence. These results enhance our understanding of the pod shattering mechanism not only in M. ruthenica but also in other leguminous plants.
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http://dx.doi.org/10.1016/j.plaphy.2022.06.013DOI Listing
June 2022

Hepatoprotective effect of phillygenin on carbon tetrachloride-induced liver fibrosis and its effects on short chain fatty acid and bile acid metabolism.

J Ethnopharmacol 2022 Jun 16;296:115478. Epub 2022 Jun 16.

State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address:

Ethnopharmacological Relevance: Forsythiae fructus, the dried fruit of Oleaceae plant Forsythia suspensa (Thunb.) Vahl, is a traditional Chinese medicine widely used in clinical practice and has a variety of pharmacological activities, such as anti-inflammation, antioxidation, and hepatoprotection.

Aim Of The Study: Phillygenin (PHI), an important fingerprint lignan component of Forsythiae fructus, has prominent hepatoprotective, anti-inflammatory and antioxidant effects. Previously, it was shown that PHI could exert anti-fibrotic effects by modulating inflammation and gut microbiota. Therefore, given the important roles of SCFAs and BAs in the development of liver fibrosis, as well as their close links with gut microbiota, we aimed to determine the protective effects of PHI on carbon tetrachloride (CCl)-induced liver fibrosis and its effects on the metabolism of SCFAs and BAs based on metabolomics.

Materials And Methods: In C57BL/6J mice, liver fibrosis model was established by intraperitoneal injection of olive oil containing 10% CCl for 4 weeks. Firstly, the mouse liver tissues were subjected to histological analysis and biochemical index assay to evaluate the protective effect of PHI on CCl-induced liver fibrosis. Subsequently, the effects of PHI on the metabolism of SCFAs and BAs in CCl-induced liver fibrosis mice were determined using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) for metabolomics analysis. Finally, the levels of the closely related proteins and genes were detected by immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR) to explore the underlying mechanisms of the protective effect of PHI on CCl-induced liver fibrosis.

Results: The histological analysis and the determination of relevant biochemical indexes of liver tissues showed that PHI could attenuate CCl-induced liver fibrosis. The metabolomic analysis on SCFAs showed that PHI could promote SCFA production in the gut of mice with CCl-induced liver fibrosis, especially acetic acid, propionic acid and butyric acid. It has been reported that the increased production of SCFAs was possibly beneficial to health. The metabolomic analysis on BAs found that PHI could restore the disturbance of BA metabolism in mice with CCl-induced liver fibrosis. The immunohistochemistry and RT-qPCR results confirmed that PHI could ameliorate intestinal epithelial barrier disruption, and reverse the expression of BA metabolism-related genes in mice with CCl-induced liver fibrosis.

Conclusions: Promoting the production of SCFAs in the gut and restoring the disturbance of BA metabolism may be the potential mechanisms by which PHI alleviated CCl-induced liver fibrosis.
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http://dx.doi.org/10.1016/j.jep.2022.115478DOI Listing
June 2022

HCV Self-Testing to Expand Testing: A Pilot Among Men Who Have Sex With Men in China.

Front Public Health 2022 31;10:903747. Epub 2022 May 31.

School of Public Health, Southern Medical University, Guangzhou, China.

Background: Hepatitis C virus self-testing (HCVST) may increase test uptake especially among marginalized key populations such as men who have sex with men (MSM). We conducted an observational study to assess the usability, acceptability and feasibility of HCVST among MSM in China.

Methods: An observational study with convenience sampling was performed among MSM in Guangzhou, China in 2019. The OraQuick® HCV Rapid Antibody Test kits were used in this study. Participants performed all 12 HCVST steps and interpreted the results in the presence of a trained observer. Usability was defined as the number and percentage of participants who completed all testing steps correctly without assistance and interpreted the results correctly. Inter-reader concordance was calculated as the percentage agreement between the results interpreted by the participant and those interpreted by a trained staff member. The same process was used to estimate inter-operator agreement between the self-testing and professional use test results. Acceptability was assessed using an interviewer-administered semi-structured questionnaire.

Results: Among 100 participants with median age 27 (interquartile range 23-30) years, 4% reported prior history of HCV testing, 41% reported using blood-based HIV self-testing in the past, 54% (95%CI: 43.7-64.0%) completed all self-testing steps correctly without assistance and interpreted the results correctly. Both the inter-reader and inter-operator concordance were excellent at 97% (95%CI: 91.5-99.4%) and 98% (95%CI: 93.0-99.8%), respectively. The majority rated the HCVST process as very easy (52%, 95%CI: 41.8-62.1%) or easy (41%, 95%CI: 31.3-51.3%), 76% (95%CI: 66.4-84.0%) were willing to use HCVST again, and 75% (95%CI: 65.3-83.1%) would recommend it to their family and friends.

Conclusions: Our findings demonstrate that oral fluid HCVST has high usability and acceptability among Chinese MSM. More implementation research is needed to plan how best to position and scale-up HCVST alongside other facility-and community-based testing approaches and ensure data linkage into health systems.
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http://dx.doi.org/10.3389/fpubh.2022.903747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194083PMC
June 2022

Identification of Prognosis-Related Molecular Subgroups and Construction of a Prognostic Prediction Model Using Immune-Related Genes in Pancreatic Cancer.

J Oncol 2022 7;2022:7117014. Epub 2022 Jun 7.

Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China.

Background: Pancreatic cancer patients with similar clinicopathological status exhibit substantially different therapeutic responses, which might be caused by the vast molecular heterogeneity of tumors. In this study, we attempted to identify specific molecular subgroups and construct a prognostic prediction model based on the expression level of immune-related genes in pancreatic cancer. The transcriptome profiling, single nucleotide variation, copy number variation, clinicopathological information, and follow-up data of pancreatic cancer patients were obtained from The Cancer Genome Atlas database. Thereafter, the immune-related genes with prognostic significance were identified for further consensus cluster analysis. The molecular characteristics and clinicopathological information were compared between the identified subgroups, and a weighted correlation network analysis was performed to identify the hub genes associated with the subgroups. Finally, the prognostic prediction model based on immune-related genes was established using the least absolute shrinkage and selection operator (LASSO) analysis.

Results: A total of 67 immune-relevant genes with prognostic significance were selected and used for the consensus cluster analysis. The total samples were divided into two groups, C1 and C2. The subgroup C1 had a significantly worse prognosis than C2, as well as lower levels of immune cell infiltration, which indicate an immunosuppressed state. The mutational rate of the cancer-related genes including , 53, and 43 was higher in the C1 subgroup. The C1 subgroup was associated with more advanced tumor grade and T stage and with higher mortality. Using LASSO regression, we developed a prognostic prediction model based on the expression levels of 19 immune-related genes, which we validated in three external data sets. In addition, we identified four potential therapeutic and prognostic biomarkers (, , , and ).

Conclusion: We identified two novel molecular subgroups of pancreatic cancer and developed a prognostic prediction model based on the expression levels of immune-related genes, which could be used in a clinical setting and could aid in unraveling the molecular processes leading to the development of pancreatic cancer.
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http://dx.doi.org/10.1155/2022/7117014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197625PMC
June 2022

Measles Epidemiology and Viral Nucleoprotein Gene Evolution in Shandong Province, China.

J Med Virol 2022 Jun 16. Epub 2022 Jun 16.

School of Life Sciences, Shandong First Medical University, Tai'an, Shandong, 271000, China.

Measles, caused by measles virus (MeV), has not been eradicated in many regions and countries, threatening human health. Thus, it is beneficial for measles elimination to understand measles epidemiology and molecular evolution of key viral genes, such as nucleoprotein (N) gene. Based on public data, measles epidemiological information and MeV N gene sequences reported in Shandong Province, China were comprehensively collected and systematically analyzed. The results showed a positive correlation between population density and measles incidence (r = + 0.31), while negative correlations were found between measles incidence and healthcare condition (r = - 0.21) as well as average routine vaccination rate (r = - 0.11). Additionally, the predominant lineage of MeV in Shandong was formed by genotype H1 strains, and the time of the most recent common ancestor of the N gene of MeV genotype H1 in Shandong traced back to 1987 (95% highest posterior density, 1984-1990) with relatively rapid evolution (mean rate, 1.267×10 substitutions/site/year). The genetic diversity of MeV N gene increased with the substantial emergence of major divergent clades of genotype H1 before 2005 and then remained relatively stable. In summary, these findings provided a significant insight into the measles elimination. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jmv.27941DOI Listing
June 2022

Metabolic Symbiosis-Blocking Nano-Combination for Tumor Vascular Normalization Treatment.

Adv Healthc Mater 2022 Jun 16:e2102724. Epub 2022 Jun 16.

State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, P. R. China.

The clinical anti-vascular endothelial growth factor (anti-VEGF) drugs and metronomic chemotherapy (MET) induced tumor vascular normalization treatment (TVNT) are easily antagonized by tumor microenvironment metabolic cross-talk between tumor cells and endothelial cells (ECs). To overcome this dilemma, nanodrug with the ability of ECs targeted glycolysis inhibition and nanodrug with the ability of tumor cell glycolysis inhibition, anti-VEGF, and MET are combined to prepare Nano-combination the pathways related to angiogenesis, tumor cell proliferation, and immunosuppression and breaking the negative sugar-lipid-protein metabolism balance in tumor microenvironment. Thus, stronger and more lasting normalized tumor vascular network and remarkable antitumor efficacy are obtained after treatment, constructing a positive feedback loop between TVNT and anti-tumor therapy. Above all, this study provides a new insight for solving the bottleneck of clinical TVNT.
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http://dx.doi.org/10.1002/adhm.202102724DOI Listing
June 2022

Ameliorative effects of chlorogenic acid on alcoholic liver injury in mice via gut microbiota informatics.

Eur J Pharmacol 2022 Jun 10;928:175096. Epub 2022 Jun 10.

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China; Synergetic Innovation Center for Food Safety and Nutrition, Jiangnan University, Wuxi, 214122, China. Electronic address:

Chlorogenic acid (CGA) is a functional phenolic acid widely used in food and medicine-related fields. It has been proved to be effective in the treatment of alcoholic liver disease (ALD). However, the exact mechanism by which CGA prevents ALD, especially from the crosstalk between gut and liver, has not been previously reported. This work was aimed to explore the protective effects of CGA against ALD and its relationships to gut-liver axis abnormalities. Experimental results showed the increased (p < 0.05) serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), low density lipoprotein (LDL), total cholesterol (TC) and triglyceride (TG) levels of mice fed with ethanol were ameliorated by supplementing with CGA. Moreover, CGA promoted the production of n-butyric acid by nearly 3 times (1.78 vs 0.62 nM, p < 0.01), a short-chain fatty acid that helps maintain the integrity of the intestinal barrier. Furthermore, CGA alleviated microbial dysbiosis, evidenced by the increased relative abundances of beneficial bacteria Muribaculaceae, Bacteroides, Alloprevotella, and Parabacteroides, and decreased that of opportunistic pathogens Eubacterium_nodatum, Eubacterium_ruminantium, and Anaerotruncus. Correlation analysis further elucidated the microbiota altered after CGA intervention was positively correlated with short-chain fatty acids and antioxidant indexes, while negatively correlated with inflammatory cytokines. In summary, these findings suggested the hepatoprotective effect of CGA was ascribed to the modulation of gut-liver axis homeostasis.
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http://dx.doi.org/10.1016/j.ejphar.2022.175096DOI Listing
June 2022

Au-Based Thin-Film Metallic Glasses for Propagating Surface Plasmon Resonance-Based Sensor Applications.

ACS Omega 2022 Jun 26;7(22):18780-18785. Epub 2022 May 26.

Department of Materials Science and Engineering, National Taiwan University, Taipei 10617, Taiwan.

We deposited Au-Cu-Si, an Au-based thin-film metallic glass (TFMG) of ∼50 nm thickness, as the activation layer for propagating surface plasmon resonance (PSPR)-based sensors on a BK7 glass substrate to substitute the commonly used gold layer. The film composition was tuned to yield the maximum Au content (∼65 at %), while the structure remained amorphous. The results showed that the Au-based TFMG could support surface plasmon resonance and gave rise to the extinction in the angle-resolved reflection spectrum. Using deionized water and ethyl alcohol with the refractive index difference of ∼0.03 as the analytes, the angle shift given by Au-based TFMG was 4° compared to 5° given by the Au film. Hence, Au-based TFMG is feasible to be used as the activation layer in PSPR-based sensors. Compared to the Au film, Au-based TFMG has the advantages of being less expensive, lacking grain boundary scattering, better adhesion to the substrate, and higher resistance to scratch and corrosion because of its amorphous structure with excellent mechanical properties.
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http://dx.doi.org/10.1021/acsomega.2c01565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178754PMC
June 2022

Better preparation is required for proactive advance care planning.

BMJ Support Palliat Care 2022 Jun 9. Epub 2022 Jun 9.

School of Nursing, Peking University, Beijing, China

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http://dx.doi.org/10.1136/bmjspcare-2022-003746DOI Listing
June 2022

Tailored Hydrogel Delivering Niobium Carbide Boosts ROS-Scavenging and Antimicrobial Activities for Diabetic Wound Healing.

Small 2022 Jun 9:e2201300. Epub 2022 Jun 9.

Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

The treatment of diabetic wounds remains challenging due to the excess levels of oxidative stress, vulnerability to bacterial infection, and persistent inflammation response during healing. The development of hydrogel wound dressings with ideal anti-inflammation, antioxidant, and anti-infective properties is an urgent clinical requirement. In the present study, an injectable thermosensitive niobium carbide (Nb C)-based hydrogel (Nb [email protected]) with antioxidative and antimicrobial activity is developed to promote diabetic wound healing. The Nb [email protected] system is composed of Nb C and a PLGA-PEG-PLGA triblock copolymer. The fabricated Nb C nanosheets (NSs) show good biocompatibility during in vitro cytotoxicity and hemocompatibility assays and in vivo toxicity assays. In vitro experiments show that Nb C NSs can efficiently eliminate reactive oxygen species (ROS), thus protecting cells in the wound from oxidative stress damage. Meanwhile, Nb C NSs also exhibit good near-infrared (NIR) photothermal antimicrobial activity against both Staphylococcus aureus and Escherichia coli. In vivo results demonstrate that Nb [email protected] promotes wound healing by attenuating ROS levels, reducing oxidative damage, eradicating bacterial infection under NIR irradiation, and accelerating angiogenesis. To summarize, the Nb [email protected] system, with its ROS-scavenging, photothermal antimicrobial and hemostatic activities, can be a promising and effective strategy for the treatment of diabetic wounds.
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http://dx.doi.org/10.1002/smll.202201300DOI Listing
June 2022

Texture analysis of SPECT myocardial perfusion provides prognostic value for dilated cardiomyopathy.

J Nucl Cardiol 2022 Jun 8. Epub 2022 Jun 8.

Department of Applied Computing, Michigan Technological University, 1400 Townsend Dr, Houghton, MI, 49931, USA.

Background: Texture analysis (TA) has demonstrated clinical values in extracting information, quantifying inhomogeneity, evaluating treatment outcomes, and predicting long-term prognosis for cardiac diseases. The aim of this study was to explore whether TA of SPECT myocardial perfusion could contribute to improving the prognosis of dilated cardiomyopathy (DCM) patients.

Methods: Eighty-eight patients were recruited in our study between 2009 and 2020 who were diagnosed with DCM and underwent single-photon emission tomography myocardial perfusion imaging (SPECT MPI). Forty TA features were obtained from quantitative analysis of SPECT imaging in subjects with myocardial perfusion at rest. All patients were divided into two groups: the all-cause death group and the survival group. The prognostic value of texture parameters was assessed by Cox regression and Kaplan-Meier analysis.

Results: Twenty-five all-cause deaths (28.4%) were observed during the follow-up (39.2±28.7 months). Compared with the survival group, NT-proBNP and total perfusion deficit (TPD) were higher and left ventricular ejection fraction (LVEF) was lower in the all-cause death group. In addition, 26 out of 40 texture parameters were significantly different between the two groups. Univariate Cox regression analysis revealed that NT-proBNP, LVEF, and 25 texture parameters were significantly associated with all-cause death. The multivariate Cox regression analysis showed that low gray-level emphasis (LGLE) (P = 0.010, HR = 4.698, 95% CI 1.457-15.145) and long-run low gray-level emphasis (LRLGE) (P =0.002, HR = 6.085, 95% CI 1.906-19.422) were independent predictors of the survival outcome. When added to clinical parameters, LVEF, TPD, and TA parameters, including LGLE and LRLGE, were incrementally associated with all-cause death (global chi-square statistic of 26.246 vs. 33.521; P = 0.028, global chi-square statistic of 26.246 vs. 34.711; P = 0.004).

Conclusion: TA based on gated SPECT MPI could discover independent prognostic predictors of all-cause death in medically treated patients with DCM. Moreover, TA parameters, including LGLE and LRLGE, independent of the total perfusion deficit of the cardiac myocardium, appeared to provide incremental prognostic value for DCM patients.
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http://dx.doi.org/10.1007/s12350-022-03006-4DOI Listing
June 2022

First in-human modified atrial septostomy combining radiofrequency ablation and balloon dilation.

Heart 2022 Jun 8. Epub 2022 Jun 8.

Department of Nuclear Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College Fuwai Hospital, Xicheng, Beijing, China.

Objective: Preclinical research suggests that the combined use of radiofrequency ablation and balloon dilation (CURB) could create stable interatrial communications without device implantation. This study examined the first in-human use of CURB for modified atrial septostomy in patients with severe pulmonary arterial hypertension (PAH).

Methods: Between July 2018 and October 2021, CURB was performed in 19 patients with severe PAH (age: 31.5±9.1 years; mean pulmonary artery pressure: 73 mm Hg (IQR: 66-92); pulmonary vascular resistance: 18.7 Wood units (IQR: 17.8-23.3)). Under guidance of intracardiac echocardiography and three-dimensional location system, (1) fossae ovalis was reconstructed and ablated point-by-point with radiofrequency; (2) then graded balloon dilation was performed after transseptal puncture and the optimal size was determined according to the level of arterial oxygen saturation (SatO); (3) radiofrequency ablation was repeated around the rims of the created fenestration. The interatrial fenestrations were followed-up serially.

Results: After CURB, the immediate fenestration size was 4.4 mm (IQR: 4.1-5.1) with intracardiac echocardiography, systolic aortic pressure increased by 10.2±6.9 mm Hg, cardiac index increased by 0.7±0.3 L/min/m and room-air resting SatO2 decreased by 6.2±1.9% (p<0.001). One patient experienced increased pericardiac effusion postoperatively; the others had no complications. On follow-up (median: 15.5 months), all interatrial communications were patent with stable size (intraclass correlation coefficient=0.96, 95%CI:0.89 to 0.99). The WHO functional class increased by 1 (IQR: 1-2) (p<0.001) with improvement of exercise capacity (+159.5 m, P<0.001).

Conclusion: The interatrial communications created with CURB in patients with severe PAH were stable and the mid-term outcomes were satisfactory.

Trial Registration Number: NCT03554330.
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http://dx.doi.org/10.1136/heartjnl-2022-321212DOI Listing
June 2022

Novel Compound Heterozygous Mutation in FSIP2 Causes Multiple Morphological Abnormalities of the Sperm Flagella (MMAF) and Male Infertility.

Reprod Sci 2022 Jun 7. Epub 2022 Jun 7.

Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China.

Multiple morphological abnormalities of the sperm flagella (MMAF), characteristic with bent, short, coiled, absent, and abnormal caliber flagella, is an important basis of male infertility. Genetic factors account for a large proportion of patients with MMAF. The fibrous sheath interacting protein 2 (FSIP2) has a significant function in the spermatogenesis and flagellar motility. In our study, a novel compound heterozygous mutation (c.1494C > A, p.C498* and c.11020_11024del, p.Tyr3675Cysfs*3) in FSIP2 gene was identified in an infertile male patient with MMAF. H&E staining presented typical MMAF phenotype and thick neck, midpiece in the patient's sperm cells. Transmission electron microscopy observation showed abnormal mitochondrial arrangement and disorganization and dysplastic of the fibrous sheath (FS), which were verified again under light microscopy. Immunofluorescence (IF) analysis of FISP2 expression showed that FSIP2 was absent in the flagellum of the patient's sperm cells. Our findings will be helpful to the precise diagnosis of MMAF and male infertility and enrich the mutational spectrum of FSIP2 gene.
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http://dx.doi.org/10.1007/s43032-022-00965-4DOI Listing
June 2022
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