Publications by authors named "Wen Yang"

965 Publications

Identification of C3 and FN1 as potential biomarkers associated with progression and prognosis for clear cell renal cell carcinoma.

BMC Cancer 2021 Oct 23;21(1):1135. Epub 2021 Oct 23.

Department of Urology, Xuzhou Central Hospital, Xuzhou, China.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most lethal urological malignancies, but the pathogenesis and prognosis of ccRCC remain obscure, which need to be better understand.

Methods: Differentially expressed genes were identified and function enrichment analyses were performed using three publicly available ccRCC gene expression profiles downloaded from the Gene Expression Omnibus database. The protein-protein interaction and the competing endogenous RNA (ceRNA) networks were visualized by Cytoscape. Multivariate Cox analysis was used to predict an optimal risk mode, and the survival analysis was performed with the Kaplan-Meier curve and log-rank test. Protein expression data were downloaded from Clinical Proteomic Tumor Analysis Consortium database and Human Protein Atlas database, and the clinical information as well as the corresponding lncRNA and miRNA expression data were obtained via The Cancer Genome Atlas database. The co-expressed genes and potential function of candidate genes were explored using data exacted from the Cancer Cell Line Encyclopedia database.

Results: Of the 1044 differentially expressed genes shared across the three datasets, 461 were upregulated, and 583 were downregulated, which significantly enriched in multiple immunoregulatory-related biological process and tumor-associated pathways, such as HIF-1, PI3K-AKT, P53 and Rap1 signaling pathways. In the most significant module, 36 hub genes were identified and were predominantly enriched in inflammatory response and immune and biotic stimulus pathways. Survival analysis and validation of the hub genes at the mRNA and protein expression levels suggested that these genes, particularly complement component 3 (C3) and fibronectin 1 (FN1), were primarily responsible for ccRCC tumorigenesis and progression. Increased expression of C3 or FN1 was also associated with advanced clinical stage, high pathological grade, and poor survival in patients with ccRCC. Univariate and multivariate Cox regression analysis qualified the expression levels of the two genes as candidate biomarkers for predicting poor survival. FN1 was potentially regulated by miR-429, miR-216b and miR-217, and constructed a bridge to C3 and C3AR1 in the ceRNA network, indicating a critical position of FN1.

Conclusions: The biomarkers C3 and FN1 could provide theoretical support for the development of a novel prognostic tool to advance ccRCC diagnosis and targeted therapy.
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http://dx.doi.org/10.1186/s12885-021-08818-0DOI Listing
October 2021

Bi-allelic variants in DNAH10 cause asthenoteratozoospermia and male infertility.

J Assist Reprod Genet 2021 Oct 16. Epub 2021 Oct 16.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.

Purpose: Multiple morphological abnormalities in the sperm flagella (MMAF) comprise a severe phenotype of asthenoteratozoospermia with reduced or absent spermatozoa motility. Whereas dozens of candidate pathogenic genes for MMAF have been identified, the genetic cause in a large proportion of patients is unknown. We attempted to identify novel genetic explanations for MMAF.

Methods: We performed whole-exome sequencing of patients with MMAF to identify pathogenic variants. The phenotypes of spermatozoa in patients carrying DNAH10 variants were investigated using haematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy. The expression and location of DNAH10 and other spermatozoa structure-related proteins were analyzed using immunofluorescence assays.

Results: We found one homozygous frameshift DNAH10 variant (NM_207437: c.2514delG:p.L839*) and one compound heterozygous DNAH10 variant (NM_207437: c.10820 T > C:p.M3607T; c.12692C > T:p.T4231I) in two patients with MMAF. These variants were absent or rare in the general population. Haematoxylin and eosin staining and scanning electron microscopy revealed the significant disruption of sperm flagella in the patients. In addition, ultrastructural analysis by transmission electron microscopy showed significant inner dynein arm (IDA) deficiency in sperm flagella. Using immunofluorescence assays, we found a significant reduction in IDA-related proteins including DNAH10 and DNAH1.

Conclusions: We identified putative novel pathogenic variants in DNAH10 for MMAF, which might advance the genetic diagnosis and clinical genetic counselling for male infertility.
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http://dx.doi.org/10.1007/s10815-021-02306-xDOI Listing
October 2021

Quantification of lectin in soybeans and soy products by liquid chromatography-tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Oct 13;1185:122987. Epub 2021 Oct 13.

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, PR China. Electronic address:

Lectin is one of the major anti-nutritional factors in soybeans and inhibits digestion of dietary protein. Here, an absolute quantification method was developed to detect lectin using synthetic peptide TTSWDLANNK as reference standard and corresponding isotope labeled peptide TTSWDLANNK (Alanine-C,N) as internal standard to normalize results. After the ground soybeans and soy products were defatted with n-hexane and extracted with extraction buffer, the crude protein extract was digested on filter membrane by trypsin. Further, the enzymatic hydrolysis peptides were quantified using liquid chromatography-tandem mass spectrometry. The synthetic reference peptide showed a detection limit of 0.27 ng/mL and a linear relationship in the range of 3.2-1000 ng/mL (r > 0.997). Correspondingly, the detect limit of lectin in soybean samples was 35.5 μg/g. The results showed that the recoveries of the lectin in spiked samples ranged from 80.9% to 108.7% with intra-day precisions (% CV) less than 9%. The method was successfully used to evaluate lectin levels in hundreds of soybean seeds from different varieties and soy products from different soybean processing techniques. Furthermore, the method may provide a potential application as a general method for the ultrasensitive detection of various protein anti-nutritional factors in food.
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http://dx.doi.org/10.1016/j.jchromb.2021.122987DOI Listing
October 2021

Circular RNA FOXP1 relieves trophoblastic cell dysfunction in recurrent pregnancy loss via the miR-143-3p/S100A11 cascade.

Bioengineered 2021 Dec;12(1):9081-9093

Department of Gynecology, The First People's Hospital of Lianyungang, Lianyungang, P.R. China.

Recurrent pregnancy loss (RPL) is closely associated with insufficient functions of trophoblastic cells. Circular RNA forkhead box P1 (circFOXP1) can regulate cell activities in different types of diseases. However, its effects on trophoblastic cells and its role in RPL development remain unknown. In this study, gene expressions were detected by RT-qPCR. Protein levels were detected by Western blotting. Trophoblastic cell viability, apoptosis, invasion, and migration were respectively analyzed via CCK-8, flow cytometry, wound healing, and transwell assays. The association between miR-143-3p and circFOXP1 or S100A11 (S100 calcium binding protein A11) was explored and confirmed by bioinformatics prediction and luciferase reporter assay. Herein, miR-143-3p was upregulated in RPL. Furthermore, miR-143-3p upregulation induced apoptosis and suppressed proliferation, epithelial-to-mesenchymal transition (EMT) process, and metastatic capabilities of trophoblastic cells; whereas, miR-143-3p inhibition exert opposite effects. MiR-143-3p targeted S100A11 and was adversely regulated by circFOXP1 expression. S100A11 inhibition partially offset the effect of miR-143-3p knockdown on trophoblastic cell viability, apoptosis, EMT, invasion, and migration. In addition, circFOXP1 competitively combined with miR-143-3p, thus regulating S100A11 expression. Moreover, circFOXP1 regulated trophoblastic cell functions through the miR-143-3p/S100A11 cascade. To sum up, our study, for the first time, demonstrated that circFOXP1 could improve dysfunction of trophoblastic cells through the miR-143-3p/S100A11 axis, providing novel biomarkers and diagnostic targets for RPL.
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http://dx.doi.org/10.1080/21655979.2021.1988374DOI Listing
December 2021

Influence of Submicron Fibrillated Cellulose Fibers from Cotton on Hydration and Microstructure of Portland Cement Paste.

Molecules 2021 Sep 26;26(19). Epub 2021 Sep 26.

State Key Laboratory of New Textile Materials & Advanced Processing Technology, College of Materials Science and Engineering, Wuhan Textile University, Wuhan 430073, China.

This paper reports the influence of submicron hydrophilic fibers on the hydration and microstructure of Portland cement paste. Submicron fibrillated cellulose (SMC) fibers was prepared by the acid hydrolysis of cotton fibers in HSO solution (55% /) for 1.5 h at a temperature of 50 °C. The SMC fibers were added into cement with a dosage of 0.03 wt.%, and the effect of SMC on the hydration and microstructure of cement paste was investigated by calorimeter analysis, XRD, FT-IR, DSC-TG, and SEM. Microcrystalline cellulose (MCC) fibers were used as the contrast admixture with the same dosage in this study. The results show that the addition of SMC fibers can accelerate the cement hydration rate during the first 20 h of the hydration process and improve the hydration process of cement paste in later stages. These results are because the scale of SMC fibers more closely matches the size of the C-S-H gel compared to MCC fibers, given that the primary role of the SMC is to provide potential heterogeneous nucleation sites for the hydration products, which is conducive to an accelerated and continuous hydration reaction. Furthermore, the induction and bridging effects of the SMC fibers make the cement paste microstructure more homogeneous and compact.
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http://dx.doi.org/10.3390/molecules26195831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510208PMC
September 2021

Effect of Hole Arrangement on Failure Mechanism of Multiple-Hole Fiber Metal Laminate under On-Axis and Off-Axis Loading.

Materials (Basel) 2021 Oct 2;14(19). Epub 2021 Oct 2.

College of Engineering, Zhejiang Normal University, Jinhua 321004, China.

Mechanical joints are commonly required in structures made of fiber metal laminate (FML), which pose a threat due to multi-site stress concentrations at rivet or bolt holes. Thus, for a reasonably designed FML joint, it is essential to characterize the failure mechanism of multiple-hole FML; however, little information about this has been found in open literature. In the present work, influences of hole arrangement and loading strategy (on-axis or off-axis) on the failure mechanism of multiple-hole FML were investigated, by performing finite element analyses and energy dissipation analyses with elastoplastic progressive damage models that took curing stress into account. Six types of specimens with holes arranged in parallel and staggered forms were designed, whose geometrical parameters were in strict accordance with those specified for composites joints. It indicated that the stress distribution, gross/net notched strength, critical fracture path, and damage evaluation process were only slightly influenced by the hole number and hole arrangement. On the other hand, they were strongly influenced by the loading strategy, due to the transition of failure domination. Results presented here can provide evidence for introducing design regulations of composite joints into the more hybrid FML, and for reasonably determining its multiple-hole strength merely based on the sing-hole specimen.
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http://dx.doi.org/10.3390/ma14195771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510313PMC
October 2021

Recent advances in immunoassays and biosensors for mycotoxins detection in feedstuffs and foods.

J Anim Sci Biotechnol 2021 Oct 11;12(1):108. Epub 2021 Oct 11.

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.

Mycotoxins are secondary metabolites produced by fungus. Many mycotoxin species are highly toxic and are frequently found in cereals and feedstuffs. So, powerful detection methods are vital and effective ways to prevent feed contamination. Traditional detection methods can no longer meet the needs of massive, real-time, simple, and fast mycotoxin monitoring. Rapid detection methods based on advanced material and sensor technology are the future trend. In this review, we highlight recent progress of mycotoxin rapid detection strategies in feedstuffs and foods, especially for simultaneous multiplex mycotoxin determination. Immunoassays, biosensors, and the prominent roles of nanomaterials are introduced. The principles of different types of recognition and signal transduction are explained, and the merits and pitfalls of these methods are compared. Furthermore, limitations and challenges of existing rapid sensing strategies and perspectives of future research are discussed.
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http://dx.doi.org/10.1186/s40104-021-00629-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504128PMC
October 2021

Insight into the effects of dislocations in nanoscale titanium niobium oxide (TiNbO) anode for boosting lithium-ion storage.

J Colloid Interface Sci 2021 Sep 27;608(Pt 1):90-102. Epub 2021 Sep 27.

Key Laboratory of Cluster Science of Ministry of Education, Beijing Key Laboratory of Photoelectronic/Electrophotonic Conversion Materials, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, PR China. Electronic address:

Defect engineering through induction of dislocations is an efficient strategy to design and develop an electrode material with enhanced electrochemical performance in energy storage technology. Yet, synthesis, comprehension, identification, and effect of dislocation in electrode materials for lithium-ion batteries (LIBs) are still elusive. Herein, we propose an ethanol-thermal method mediated with surfactant-template and subsequent annealing under air atmosphere to induce dislocation into titanium niobium oxide (TiNbO), resultant nanoscale-dislocated-TiNbO (Nano-dl-TNO). High-resolution transmission electron microscope (HRTEM), fast Fourier transform (FFT), and Geometrical phase analysis (GPA) denote that the high dislocation density engraved with stacking faults forms into the TiNbO lattice. The presence of dislocation could offer an additional active site for lithium-ion storage and tune the electrical and ionic properties of the TiNbO. The resultant Nano-dl-TNO delivers superior rate capability, high specific capacity, better cycling stability, and making TiNbO a suitable candidate among fast-charging anode materials for lithium-ion batteries. Moreover, In-situ High-resolution transmission electron microscope (HRTEM) and Geometrical phase analysis (GPA) evinces that the removal of the dislocated area in the Nano-dl-TNO leads to the contraction of the lattice, alleviation of the total volume expansion, causing the symmetrization and preserves structural stability. The present findings and designed approach reveal the rose-colored perspective of dislocation engineering into mixed transition metal oxides as next-generation anodes for advanced lithium-ion batteries and all-solid-state lithium-ion batteries.
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http://dx.doi.org/10.1016/j.jcis.2021.09.149DOI Listing
September 2021

Dedifferentiated liposarcoma with abrupt transition of low-grade and high-grade dedifferentiation: A rare case report.

Int J Immunopathol Pharmacol 2021 Jan-Dec;35:20587384211048565

Departments of Pathology, 74678Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

Dedifferentiated liposarcoma is a unique subtype of liposarcoma, which has obvious histological heterogeneity. In affected patients, the condition typically manifests as the dedifferentiation of high-grade histological morphology, but it may also manifest as the dedifferentiation of low-grade histological morphology. In some cases, unique histological or immunophenotypic characteristics are observed. We describe, herein, a rare case of dedifferentiated liposarcoma, in which the high-grade and low-grade dedifferentiated components coexisted with a relatively sharp transition in pathology.
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http://dx.doi.org/10.1177/20587384211048565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504230PMC
October 2021

Object Detection in Aerial Images: A Large-Scale Benchmark and Challenges.

IEEE Trans Pattern Anal Mach Intell 2021 Oct 6;PP. Epub 2021 Oct 6.

In the past decade, object detection has achieved significant progress in natural images but not in aerial images, due to the massive variations in the scale and orientation of objects caused by the bird's-eye view of aerial images. More importantly, the lack of large-scale benchmarks has become a major obstacle to the development of object detection in aerial images (ODAI). In this paper, we present a large-scale Dataset of Object deTection in Aerial images (DOTA) and comprehensive baselines for ODAI. The proposed DOTA dataset contains 1,793,658 object instances of 18 categories of oriented-bounding-box annotations collected from 11,268 aerial images. Based on this large-scale and well-annotated dataset, we build baselines covering 10 state-of-the-art algorithms with over 70 configurations, where the speed and accuracy performances of each model have been evaluated. Furthermore, we provide a code library for ODAI and build a website for evaluating different algorithms. Previous challenges run on DOTA have attracted more than 1300 teams worldwide. We believe that the expanded large-scale DOTA dataset, the extensive baselines, the code library and the challenges can facilitate the designs of robust algorithms and reproducible research on the problem of object detection in aerial images.
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http://dx.doi.org/10.1109/TPAMI.2021.3117983DOI Listing
October 2021

Nodular fasciitis of the breast: Report of two cases illustrating the diagnostic implications for USP6 gene rearrangement and brief review of the literature.

Exp Mol Pathol 2021 Sep 28;123:104690. Epub 2021 Sep 28.

Department of Breast Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, China. Electronic address:

Nodular fasciitis is a benign, self-limited, pseudosarcomatous neoplasm that is cytogenetically characterized by recurrent USP6 gene rearrangement. Involvement of the breast by nodular fasciitis is very rare with only a few documented cases. It can clinically, radiologically and histologically mimic a malignancy, posing significant diagnostic challenges to clinicians, radiologists, and pathologists. In this study, we report 2 cases of nodular fasciitis occurring in the female breast, reviewing the literature and emphasizing the application of fluorescence in situ hybridization analysis of USP6 gene rearrangement in its diagnosis and differential diagnosis.
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http://dx.doi.org/10.1016/j.yexmp.2021.104690DOI Listing
September 2021

Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature.

Open Med (Wars) 2021 9;16(1):1356-1363. Epub 2021 Sep 9.

Department of Pathology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, No. 158, Shangtang Road, Hangzhou, 310014, Zhejiang, People's Republic of China.

Peritoneal loose body (PLB) is a rare clinical entity. It is generally agreed that the most common origin of the loose bodies is appendix epiploica. We here report a case of PLB that looks like a "boiled egg," which was misdiagnosed preoperatively as a lesion of hepatic origin and was confirmed by operation and postoperative pathology. PLBs are rare entities, a good understanding of their specific imaging features can help prevent misdiagnosis, but sometimes an accurate preoperative diagnosis is still difficult to achieve. Exploratory laparoscopy is a recommended method for management of PLBs.
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http://dx.doi.org/10.1515/med-2021-0351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435557PMC
September 2021

Small-Molecule Fluorogenic Probe for the Detection of Mitochondrial Temperature .

Anal Chem 2021 10 28;93(40):13417-13420. Epub 2021 Sep 28.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.

Mitochondria, as energy factories, participate in many metabolic processes and play vital roles in cell life. Most human diseases are caused by mitochondrial dysfunction, and mitochondrial temperature is an important indicator of mitochondrial function. Despite the biological importance of mitochondria, there are few tools for detecting changes in mitochondrial temperature in living organisms. Here, we report on a thermosensitive rhodamine B (RhB)-derived fluorogenic probe (RhBIV) that enables fluorescent labeling of cell mitochondria at concentrations as low as 1 μM. We demonstrate that this probe exhibits a temperature-dependent response in cell mitochondria. Furthermore, in mice, it has a long half-life () and is primarily enriched in the liver. This unique thermosensitive probe offers a simple, nondestructive method for longitudinal monitoring of mitochondrial temperature both and to elucidate fundamental physiological and pathological processes related to mitochondrial function.
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http://dx.doi.org/10.1021/acs.analchem.1c03554DOI Listing
October 2021

Discrimination of active and inactive substances in cytotoxicity based on Tox21 10K compound library: Structure alert and mode of action.

Toxicology 2021 Oct 13;462:152948. Epub 2021 Sep 13.

Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, UF Genetics Institute, Interdisciplinary Program in Biomedical Sciences Neuroscience, University of Florida, Gainesville, FL, 32611, USA.

In vitro cytotoxicity assay is an ideal alternative method for the in vivo toxicity in the risk assessment of pollutants in environment. However, modes of action (MOAs) of cytotoxicity have not been investigated for a wide range of compounds. In this paper, binomial and recursive partitioning analysis were carried out between the cytotoxicity and molecular descriptors for 8981 compounds. The results showed that cytotoxicity is strongly related to the chemical hydrophobicity and excess molar refraction, indicating the bio-uptake and chemical-receptor interaction through π and n electron pair play important roles in the cytotoxicity. The decision tree derived from recursive partitioning analysis revealed that the studied compounds could be divided into 25 groups and their structural characteristics could be used as structure alert to identify active and inactive compounds in cytotoxicity. The descriptors used in the decision tree revealed that chemical ionization and bioavailability could affect the cytotoxicity for ionizable and highly hydrophobic compounds. Comparison of MOAs based on Verhaar's classification scheme showed that many inert or less inert compounds were inactive substance, and many reactive or specifically-acting compounds were active substances in the cytotoxicity. In vitro toxicity assay instead of in vivo toxicity assay can be used in the environmental hazard and risk assessment of organic pollutants. The descriptors used in the binomial equation and decision tree reveal that chemical hydrophobicity, ionization and solubility play very important roles for identification of active and inactive compounds. The results obtained in this paper are valuable for understanding the modes of action in cytotoxicity and in vivo-in vitro toxicity relationship.
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http://dx.doi.org/10.1016/j.tox.2021.152948DOI Listing
October 2021

Corrigendum: LncRNA NBR2 Inhibits the Malignancy of Thyroid Cancer, Associated With Enhancing the AMPK Signaling.

Front Oncol 2021 27;11:759471. Epub 2021 Aug 27.

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

[This corrects the article DOI: 10.3389/fonc.2020.00956.].
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http://dx.doi.org/10.3389/fonc.2021.759471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430396PMC
August 2021

Prevalence of Latent Tuberculosis Infection Among Healthy Young Children and Adolescents and a Two-step Approach for the Diagnosis of Tuberculosis Infection in Chengdu, China.

Pediatr Infect Dis J 2021 Sep 9. Epub 2021 Sep 9.

From the Department of Pediatrics, West China Second University Hospital, Sichuan University; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education; Chengdu Chenghua District Maternal and Child Health Hospital; Department of Pediatrics, Chengdu Second People's Hospital; and Department of Ultrasound, West China Second University Hospital, Sichuan University, Chengdu, China.

Background: China has a high burden of tuberculosis and latent tuberculosis infection (LTBI). The aim of this study was to estimate the prevalence of LTBI among healthy young children and adolescents and test a 2-step approach to explore the threshold for the diagnosis of tuberculosis infection in Chengdu, China.

Methods: Healthy preschool children and school-going children in Chengdu, Sichuan Province, were screened for LTBI using the tuberculin skin test (TST). Preschool children with TST ≥ 5 mm also underwent interferon-γ release assay (IGRA) to explore the threshold of this 2-step approach.

Results: In total, 5667 healthy young children and adolescents completed TST test between July 2020 and January 2021 and were included in the present analysis. The age of the participants ranged from 2.4 to 18 years (median 7.25 ± 4.514 years), of which 2093 (36.9%) were younger than 5 years. The overall prevalence of LTBI was 6.37% and 6.64% in children younger than 5 years old. Fourteen of the 341 preschool children with TST ≥5 mm were interferon-γ release assay positive, of which 4 showed a TST result of 5-10 mm, and 6 preschool children received preventive treatment for LTBI.

Conclusions: Healthy young children and adolescents should also be considered as important target populations for LTBI screening. TST can be recommended for first-line screening as part of a 2-step approach for LTBI screening using a positive threshold of 5 mm.
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http://dx.doi.org/10.1097/INF.0000000000003338DOI Listing
September 2021

Long-term stability, high strength, and 3D printable alginate hydrogel for cartilage tissue engineering application.

Biomed Mater 2021 09 28;16(6). Epub 2021 Sep 28.

Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, People's Republic of China.

Cartilage damage is one of the main causes of disability, and 3D bioprinting technology can produce complex structures that are particularly suitable for constructing a customized and irregular tissue engineering scaffold for cartilage repair. Alginate is an attractive biomaterial for bioinks because of its good biological safety profile and fast ionic gelation. However, ionically crosslinked alginate hydrogels are recognized as lacking enough mechanical property and long-term stability due to ion exchange. Here, we developed a double crosslinked alginate (DC-Alg) hydrogel for 3D bioprinting, and human umbilical cord mesenchymal stem cells (huMSCs) could differentiate into chondrocytes on its printed 3D scaffold after 4 weeks' culture. We performed sequential modification of alginate with L-cysteine and 5-norbornene-2-methylamine, and the DC-Alg hydrogels were obtained in the presence of CaCland ultraviolet light with stronger mechanical properties than those of the single ionic crosslinked alginate hydrogels, which was similar to natural cartilage. They also had better stability and could be maintained in DMEM medium for over 1 month, as well good viability for huMSCs. Moreover, the DC-Alg as 3D printing inks demonstrated a better printing accuracy (∼200 µm). After 4 weeks culture of huMSCs in the 3D printed DC-Alg scaffolds, the expressions of chondrogenic genes such as99) were obviously observed, indicating the differentiation of huMSCs into cartilage. Immumohistochemical staining analysis further exhibited cartilage tissue developed well in the 3D printed scaffolds. Our study is the first demonstration of DC-Alg in 3D printing for MSC differentiation into cartilage, which shows a potential application in cartilage defect repair.
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http://dx.doi.org/10.1088/1748-605X/ac2595DOI Listing
September 2021

Nanoplasmonic Sandwich Immunoassay for Tumor-Derived Exosome Detection and Exosomal PD-L1 Profiling.

ACS Sens 2021 09 8;6(9):3308-3319. Epub 2021 Sep 8.

Materials Research and Education Center, Materials Engineering, Department of Mechanical Engineering, Auburn University, Auburn, Alabama 36849, United States.

Tumor-derived exosomes play a vital role in the process of cancer development. Quantitative analysis of exosomes and exosome-shuttled proteins would be of immense value in understanding cancer progression and generating reliable predictive biomarkers for cancer diagnosis and treatment. Recent studies have indicated the critical role of exosomal programmed death ligand 1 (PD-L1) in immune checkpoint therapy and its application as a patient stratification biomarker in cancer immunotherapy. Here, we present a nanoplasmonic exosome immunoassay utilizing gold-silver ([email protected]) core-shell nanobipyramids and gold nanorods, which form sandwich immune complexes with target exosomes. The immunoassay generates a distinct plasmonic signal pattern unique to exosomes with specific exosomal PD-L1 expression, allowing rapid, highly sensitive exosome detection and accurate identification of PD-L1 exosome subtypes in a single assay. The developed nanoplasmonic sandwich immunoassay provides a novel and viable approach for tumor cell-derived exosome detection and analysis with quantitative molecular details of key exosomal proteins, manifesting its great potential as a transformative diagnostic tool for early cancer detection, prognosis, and post-treatment monitoring.
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http://dx.doi.org/10.1021/acssensors.1c01101DOI Listing
September 2021

One severe case of congenital toxoplasmosis in China with good response to azithromycin.

BMC Infect Dis 2021 Sep 6;21(1):920. Epub 2021 Sep 6.

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

Background: Most infants infected with Toxoplasma gondii are completely asymptomatic at birth, yet they may develop ocular and neurological sequelae in the first few months of life. Cases of congenital toxoplasmosis with severe jaundice early after birth combined with pancytopenia and splenomegaly are extremely rare. Here, we report on a rare case of congenital toxoplasmosis presenting with severe jaundice and hemolysis early after birth combined with pancytopenia and splenomegaly.

Case Presentation: A male preterm infant with severe jaundice and splenomegaly was admitted to our department. Laboratory examinations revealed severe hyperbilirubinemia, increased reticulocytes, and pancytopenia. After comprehensive analysis and examination, the final diagnosis was congenital toxoplasmosis, and the infant was treated with azithromycin and subsequently trimethoprim-sulfamethoxazole. Regular follow-up revealed congenital toxoplasmosis in both eyes, which was surgically treated, while neurofunctional assessment results were unremarkable. In this case of congenital toxoplasmosis combined with severe jaundice, we treated the infant with two courses of azithromycin, followed by trimethoprim-sulfamethoxazole after the jaundice resolved. Clinical follow-up indicated that this treatment was effective with few side effects; thus, this report may serve as a valuable clinical reference.

Conclusions: Timely diagnosis and adequate treatment are closely associated with congenital toxoplasmosis-related prognosis. Infants with congenital toxoplasmosis require long-term follow-up, focusing on nervous system development and ophthalmology.
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http://dx.doi.org/10.1186/s12879-021-06619-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422759PMC
September 2021

Validation of the 2020 AHA/ACC Risk Stratification for Sudden Cardiac Death in Chinese Patients With Hypertrophic Cardiomyopathy.

Front Cardiovasc Med 2021 17;8:691653. Epub 2021 Aug 17.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Sudden cardiac death (SCD) is a common cause of death in hypertrophic cardiomyopathy (HCM), but identification of patients at a high risk of SCD is challenging. The study aimed to validate the three SCD risk stratifications recommended by the 2011 ACCF/AHA guideline, the 2014 ESC guideline, and the 2020 AHA/ACC guideline in Chinese HCM patients. The study population consisted of a consecutive cohort of 511 patients with HCM without a history of SCD event. The endpoint was a composite of SCD or an equivalent event (appropriate implantable cardioverter defibrillator therapy or successful resuscitation after cardiac arrest). During a follow-up of 4.7 ± 1.7 years, 15 patients (2.9%) reached the SCD endpoint and 12 (2.3%) were protected by implantable cardioverter defibrillator for primary prevention. A total of 13 (2.8%) patients experiencing SCD events were misclassified as low-risk patients by the 2011 ACCF/AHA guideline, 12 (2.3%) by the 2014 ESC model, and 7 (1.6%) by the 2020 AHA/ACC guideline. The SCD risk stratification in the 2020 AHA/ACC guideline showed greater area under the curve (0.71; 95% CI 0.56-0.87, < 0.001) than the one in the 2011 ACCF/AHA guideline (0.52; 95% CI 0.37-0.67, = 0.76) and 2014 ESC guideline (0.68; 95% CI 0.54-0.81, = 0.02). The SCD risk stratification recommended by the 2020 AHA/ACC guideline showed a better discrimination than previous stratifications in Chinese patients with HCM. A larger multicenter, independent, and prospective study with long-term follow-up would be warranted to validate our result.
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http://dx.doi.org/10.3389/fcvm.2021.691653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415905PMC
August 2021

Non-apoptotic function of caspase-8 confers prostate cancer enzalutamide resistance via NF-κB activation.

Cell Death Dis 2021 09 4;12(9):833. Epub 2021 Sep 4.

Department of Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.

Caspase-8 is a unique member of caspases with a dual role in cell death and survival. Caspase-8 expression is often lost in some tumors, but increased in others, indicating a potential pro-survival function in cancer. By analyzing transcriptome of enzalutamide-resistant prostate cancer cells, we found that resistance was conferred by a mild caspase-8 upregulation that in turn led to NF-κB activation and the subsequent upregulation of the downstream IL-8. Mechanistically, we found that the pro-survival and enzalutamide-resistance-promoting features of caspase-8 were independent of its proteolytic activity, using a catalytically-inactive caspase-8 mutant. We further demonstrated that caspase-8 pro-apoptotic function was inhibited via cFLIP binding. Moreover, high caspase-8 expression was correlated with a worse prognosis in prostate cancer patients. Collectively, our work demonstrates that enzalutamide-resistance is mediated by caspase-8 upregulation and the consequent increase in NF-κB/IL-8 mediated survival signaling, highlighting caspase-8 and NF-κB as potential therapeutic targets to overcome enzalutamide-resistance in CRPC.
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http://dx.doi.org/10.1038/s41419-021-04126-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418603PMC
September 2021

DNA-Templated Glycan Labeling for Monitoring Receptor Spatial Distribution in Living Cells.

Anal Chem 2021 09 2;93(36):12265-12272. Epub 2021 Sep 2.

MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350108, People's Republic of China.

Tracking the spatial distribution of receptor tyrosine kinases in their native environment contributes to understanding the homeostatic or pathological states at a molecular level. Conjugation of DNA tags to a specific receptor is a powerful tool for monitoring receptor spatial distribution. However, long-term stable trafficking in live cells without interfering with the intrinsic receptor function remains a challenge. Here, we report a general DNA-templated glycan labeling strategy to track spatial distribution of a specific receptor in living cells. Different from existing target-selective covalent methods, the DNA tags were incorporated in glycan of a specific receptor via aptamer-assisted metabolic glycan labeling, thus resulting in minimal perturbation to the receptor's biological function. As proof of concept, covalent tagging of MET, HER2, and EGFR was achieved, and then the spatial distribution was successfully monitored, including homo-/heterodimerization and internalization. Overall, the proposed strategy will greatly aid in investigating receptor dynamics and is conducive to understanding their biological function in the native environment.
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http://dx.doi.org/10.1021/acs.analchem.1c01815DOI Listing
September 2021

Interactions between Prepregnancy Overweight and Passive Smoking for Macrosomia and Large for Gestational Age in Chinese Pregnant Women.

Obes Facts 2021 20;14(5):520-530. Epub 2021 Aug 20.

Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.

Introduction: Previous analysis showed that passive smoking and overweight were associated with an increased risk of gestational diabetes mellitus (GDM) in a synergistic manner, while GDM increased the risk of macrosomia/large for gestational age (LGA). This study aimed to examine any interactive effects between passive smoking and overweight/obesity on risk of macrosomia/LGA.

Methods: From 2010 to 2012, 22,302 pregnant women registered for pregnancy at a primary hospital in Tianjin, China. Data were collected longitudinally; that is, from their first antenatal care visit, at the glucose challenge test (GCT) time (24-28 weeks of gestation) and at delivery. Passive smoking was self-reported. Macrosomia was defined as birth weight ≥4,000 g. Binary logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction was used to test the synergistic effect.

Results: Passive smokers accounted for 57.4% of women (n = 8,230). Using nonpassive smoking and prepregnancy body mass index (BMI) <24.0 kg/m2 as the reference, the adjusted ORs of overweight alone and passive smoking alone for macrosomia were 2.39 (95% CI: 2.11-2.71) and 1.17 (95% CI: 1.04-1.32). Copresence of passive smoking and prepregnancy BMI ≥24.0 kg/m2 increased the OR to 2.70 (95% CI: 2.28-3.20), with a significant additive interaction. After further adjustment for GDM or GCT, the OR of copresence of both risk factors was slightly attenuated to 2.52 (2.13-3.00) and 2.51 (2.11-2.98), with significant additive interaction. However, the additive interaction between prepregnancy overweight/obesity and passive smoking for LGA was nonsignificant.

Conclusions: Prepregnancy overweight/obesity was associated with an increased risk of macrosomia in Chinese women synergistically with passive smoking during pregnancy, and most of the association was not modified by hyperglycemia during pregnancy.
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http://dx.doi.org/10.1159/000517846DOI Listing
August 2021

Design, synthesis, and biological evaluation of benzo[b]thiophene 1,1-dioxide derivatives as potent STAT3 inhibitors.

Chem Biol Drug Des 2021 Aug 20. Epub 2021 Aug 20.

Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

As a member of the signal transducer and activator of transcription (STAT) family, STAT3 plays a critical role in several biological pathways such as cell proliferation, migration, survival, and differentiation. Due to abnormal continuous activation in tumors, inhibition of STAT3 has emerged as an attractive approach for the treatment of various cancer cells. Herein, we report a series of novel STAT3 inhibitors based on benzo[b]thiophene 1,1-dioxide scaffold and evaluated their anticancer potency. Among them, compound 8b exhibited the best activity against cancer cells. Compound 8b induced apoptosis and blocked the cell cycle. Meanwhile, 8b reduced intracellular ROS content and caused the loss of mitochondrial membrane potential. Further research revealed that 8b significantly blocked STAT3 phosphorylation and STAT3-dependent dual-luciferase reporter gene experiments showed that compound 8b has a marked inhibition of STAT3-mediated Firefly luciferase activity. Molecular modeling studies revealed compound 8b occupied the pocket well with the SH2 domain in a favorable conformation.
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http://dx.doi.org/10.1111/cbdd.13939DOI Listing
August 2021

Activatable photoacoustic/fluorescent dual-modal probe for monitoring of drug-induced liver hypoxia in vivo.

Chem Commun (Camb) 2021 Sep 9;57(69):8644-8647. Epub 2021 Aug 9.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China.

Effective monitoring of liver hypoxia status is crucial for the detection and treatment of drug-induced liver injury. Here, a novel photoacoustic and fluorescent dual-modal probe (NO-CS) was rationally developed and applied to image isoniazid-induced liver hypoxia through detecting the over-expressed nitroreductase.
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http://dx.doi.org/10.1039/d1cc02999aDOI Listing
September 2021

A 51-Year-Old Man With Right Atrial Neoplasm Presenting With Syncope and Shock.

Chest 2021 Aug;160(2):e237-e241

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

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http://dx.doi.org/10.1016/j.chest.2020.08.2141DOI Listing
August 2021

Near-infrared light triggered activation of pro-drug combination cancer therapy and induction of immunogenic cell death.

Int J Pharm 2021 Sep 4;607:120972. Epub 2021 Aug 4.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849 USA. Electronic address:

Disulfiram copper complex [Cu(DDC)] nanoparticles have been explored as promising anticancer agents but with concerns of toxic side effects. To improve tumor specificity and enhance anticancer efficacy, we developed a novel [copper sulfide nanoparticle (CuS NP) + disulfiram prodrug (DQ) micelle + near-infrared (NIR) laser] (CDL) combination therapy. DQ, a reactive oxygen species (ROS)-responsive prodrug, can be selectively activated at the tumor site with elevated ROS to release DDC and form Cu(DDC)in situ. The CuS NP + NIR laser treatment can effectively increase the intra-tumor ROS levels and efficiently activate the DQ prodrug. The CDL therapy kills cancer cells through multiple mechanisms, including ROS amplification cascade and Cu(DDC) chemotherapy. NIR light-triggered tumor-specific "nontoxic-to-toxic" transition can significantly improve the specificity of anticancer effects and reduce systemic toxicity. Also, CDL therapy can effectively induce immunogenic cell death (ICD) and has the potential of eliciting antitumor immunity.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120972DOI Listing
September 2021

The effectiveness of adding guided growth to soft tissue release in treating spastic hip displacement.

J Orthop Sci 2021 Aug 3. Epub 2021 Aug 3.

Department of Pediatric Orthopedics, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan. Electronic address:

Background: Guided growth at the proximal femur using one transphyseal screw corrects coxa valga and improves hip displacement in cerebral palsy. This study aimed to validate the effects of adding guided growth (GG) to soft tissue release (STR), in terms of decreasing the migration percentage (MP), compared to those with soft tissue alone.

Methods: This retrospective study comprised patients with cerebral palsy who underwent soft tissue release alone (Group STR) or soft tissue release plus guided growth (Group GG) for hip displacement (mean age, 8.1 years; mean follow-up, 4.9 years). Difference in the MP and rate of controlling MP <40% at 2 years postoperatively and rate of revision surgeries at 5 years postoperatively were compared between the groups.

Results: The two groups were comparable in age, side, and gross motor function level, but Group GG (n = 24) had more severe hip displacement preoperatively than did Group STR (n = 64). Group GG had a significantly greater 2-year decrease in the MP (-14.8% vs. -11.8%, p < 0.05) than did Group STR. Among patients with a pre-operative MP >50%, the rate of MP <40% was greater in Group GG (73%) than in Group STR (41%). Revision surgeries, mainly repeated guided growth and soft tissue release, were comparable between the groups.

Conclusions: This is the first comparative study to support adding guided growth to soft tissue release, as it results in greater improvements in hip displacement than that with soft tissue release alone. Non-ambulatory patients or severe hip displacement with MP 50%-70% could benefit from this less aggressive surgery by controlling the MP under 40% without femoral osteotomy.
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http://dx.doi.org/10.1016/j.jos.2021.06.019DOI Listing
August 2021
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