Publications by authors named "Yue Huang"

874 Publications

Quality Management of Pulmonary Nodule Radiology Reports Based on Natural Language Processing.

Bioengineering (Basel) 2022 Jun 1;9(6). Epub 2022 Jun 1.

Information Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.

To investigate the feasibility of automated follow-up recommendations based on findings in radiology reports, this paper proposed a Natural Language Processing model specific for Pulmonary Nodule Radiology Reports. Unstructured findings used to describe pulmonary nodules in 48,091 radiology reports were processed in this study. We established an NLP model to extract information entities from findings of radiology reports, using deep learning and conditional random-field algorithms. Subsequently, we constructed a knowledge graph comprising 168 entities and four relationships, based on the export recommendations of the internationally renowned Fleischner Society for pulmonary nodules. These were employed in combination with rule templates to automatically generate follow-up recommendations. The automatically generated recommendations were then compared to the impression part of the reports to evaluate the matching rate of proper follow ups in the current situation. The NLP model identified eight types of entities with a recognition accuracy of up to 94.22%. A total of 43,898 out of 48,091 clinical reports were judged to contain appropriate follow-up recommendations, corresponding to the matching rate of 91.28%. The results show that NLP can be used on Chinese radiology reports to extract structured information at the content level, thereby realizing the prompt and intelligent follow-up suggestion generation or post-quality management of follow-up recommendations.
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http://dx.doi.org/10.3390/bioengineering9060244DOI Listing
June 2022

PCB153 suppressed autophagy via PI3K/Akt/mTOR and RICTOR/Akt/mTOR signaling by the upregulation of microRNA-155 in rat primary chondrocytes.

Toxicol Appl Pharmacol 2022 Jun 19:116135. Epub 2022 Jun 19.

Department of Orthopedics, Shengjing Hospital, China Medical University, 110004, China. Electronic address:

Polychlorinated biphenyls (PCBs) are a typical type of persistent organic pollutant. PCB exposure is associated to the occurrence and development of osteoarthritis (OA); however, the involved mechanisms have yet to be elucidated. Here, we investigated the pro-osteoarthritic effect of 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl (PCB153), and the involvement of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) and the RICTOR/Akt/mTOR signaling pathways. PCB153 of 20 and 30 μM increased the expression of MMP13 and decreased the expression of type II collagen, in a concentration-dependent manner. PCB153 treatment reduced the expression of Beclin 1 and LC3B, but increased the expression of p62 by upregulating miR-155 levels. PCB153 treatment activated the PI3K/Akt/mTOR signaling pathway by upregulating miR-155 levels. RICTOR was involved in activating the Akt/mTOR signaling pathway, and was also regulated by miR-155. In conclusion, PCB153 could promote the degradation of the extracellular matrix of chondrocytes by upregulating miR-155 via a mechanism related to the activation of the PI3K/Akt/mTOR and RICTOR/Akt/mTOR signaling pathway, which suppressed autophagy and facilitated the development of OA. MiR-155 may represent potential therapeutic targets to alleviate the development of OA.
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http://dx.doi.org/10.1016/j.taap.2022.116135DOI Listing
June 2022

Helicobacter pylori promotes gastric cancer progression through the tumor microenvironment.

Appl Microbiol Biotechnol 2022 Jun 20. Epub 2022 Jun 20.

School of Medicine, Jiangsu University, 301 Xuefu Road, 212013, Zhenjiang, China.

Gastric cancer (GC) is a leading type of cancer. Although immunotherapy has yielded important recent progress in the treatment of GC, the prognosis remains poor due to drug resistance and frequent recurrence and metastasis. There are multiple known risk factors for GC, and infection with Helicobacter pylori is one of the most significant. The mechanisms underlying the associations of H. pylori and GC remain unclear, but it is well known that infection can alter the tumor microenvironment (TME). The TME and the tumor itself constitute a complete ecosystem, and the TME plays critical roles in tumor progression, metastasis, and drug resistance. H. pylori infection can act synergistically with the TME to cause DNA damage and abnormal expression of multiple genes and activation of signaling pathways. It also modulates the host immune system in ways that enhance the proliferation and metastasis of tumor cells, promote epithelial-mesenchymal transition, inhibit apoptosis, and provide energy support for tumor growth. This review elaborates myriad ways that H. pylori infections promote the occurrence and progression of GC by influencing the TME, providing new directions for immunotherapy treatments for this important disease. KEY POINTS: • H. pylori infections cause DNA damage and affect the repair of the TME to DNA damage. • H. pylori infections regulate oncogenes or activate the oncogenic signaling pathways. • H. pylori infections modulate the immune system within the TME.
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http://dx.doi.org/10.1007/s00253-022-12011-zDOI Listing
June 2022

Myeloid Angiotensin II Type 1 Receptor Mediates Macrophage Polarization and Promotes Vascular Injury in DOCA/Salt Hypertensive Mice.

Front Pharmacol 2022 3;13:879693. Epub 2022 Jun 3.

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

Activation of the renin-angiotensin system has been implicated in hypertension. Angiotensin (Ang) II is a potent proinflammatory mediator. The present study investigated the role of myeloid angiotensin type 1 receptor (AT1R) in control of macrophage phenotype and vascular injury in deoxycorticosterone acetate (DOCA)/salt hypertension. In human THP-1/macrophages, Ang II increased mRNA expressions of M1 cytokines and decreased M2 cytokine expressions. Overexpression of AT1R further increased Ang II-induced expressions of M1 cytokines and decreased M2 cytokines. Silenced AT1R reversed Ang II-induced changes in M1 and M2 cytokines. Ang II upregulated hypoxia-inducible factor (HIF)1α, toll-like receptor (TLR)4, and the ratio of pIB/IB, which were prevented by silenced AT1R. Silenced HIF1α prevented Ang II activation of the TLR4/NFB pathway. Furthermore, Ang II increased HIF1α reactive oxygen species-dependent reduction in prolyl hydroxylase domain protein 2 (PHD2) expression. The expressions of AT1R and HIF1α and the ratio of pIB/IB were upregulated in the peritoneal macrophages of DOCA hypertensive mice, and the specific deletion of myeloid AT1R attenuated cardiac and vascular injury and vascular oxidative stress, reduced the recruitment of macrophages and M1 cytokine expressions, and improved endothelial function without significant reduction in blood pressure. Our results demonstrate that Ang II/AT1R controls the macrophage phenotype stimulating the HIF1α/NFB pathway, and specific myeloid AT1R KO improves endothelial function, vascular inflammation, and injury in salt-sensitive hypertension. The results support the notion that myeloid AT1R plays an important role in the regulation of the macrophage phenotype, and dysfunction of this receptor may promote vascular dysfunction and injury in salt-sensitive hypertension.
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http://dx.doi.org/10.3389/fphar.2022.879693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204513PMC
June 2022

YTHDF2 promotes intrahepatic cholangiocarcinoma progression and desensitises cisplatin treatment by increasing CDKN1B mRNA degradation.

Clin Transl Med 2022 Jun;12(6):e848

Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer with exceedingly poor prognosis, and chemoresistance is a huge challenge for treatment. N6-methyladenosine (m A) modification plays an important role in the progression and chemoresistance of cancers. We aimed to investigate the oncogenic function and therapeutic significance of the m A binding protein, YTH domain family 2 (YTHDF2), in ICC progression and cisplatin-based chemotherapy.

Methods: Several independent data sets were used to assess the expression of YTHDF2 in ICC, particularly in chemoresistant ICC. Knockdown and overexpression were used to evaluate the effects of YTHDF2 on tumourigenesis and cisplatin response in ICC. Multi-omics sequencing was performed to identify target genes. RIP, dual luciferase reporter, RNA stability experiment and loss-of-function assays were conducted to study the mechanisms underlying the oncogenic function of YTHDF2. Furthermore, patient-derived xenograft (PDX) model was established to determine the effect of combination treatment of YTHDF2 siRNA and cisplatin in ICC.

Results: Our study showed that YTHDF2 was upregulated in ICC tissues, particularly in chemoresistant ICC tissues, and correlated with poor prognosis. Furthermore, silencing YTHDF2 led to inhibited proliferation, promoted apoptosis and G0/G1 cell cycle arrest. Its downregulation also enhanced DNA damage and sensitised ICC cells to cisplatin. YTHDF2 overexpression exerted the opposite results. Integration analysis using RNA-seq, MeRIP-seq and anti-YTHDF2 RIP-seq elucidated the role of YTHDF2 in tumourigenesis and cisplatin-desensitising function by promoting the degradation of cyclin-dependent kinase inhibitor 1B (CDKN1B) mRNA in an m A-dependent manner. Downregulation of CDKN1B increased the YTHDF2 silencing-induced influence on tumourigenesis and cisplatin response to ICC. In addition, the combination treatment of YTHDF2 siRNA and cisplatin significantly enhanced the anti-tumour effect of cisplatin in a chemoresistant ICC PDX model.

Conclusions: YTHDF2 exhibits tumour oncogenic and cisplatin-desensitising properties, which may offer insight into the development of novel combination therapeutic strategies for ICC.
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http://dx.doi.org/10.1002/ctm2.848DOI Listing
June 2022

Characteristics of Pupil Offset in Young Asian Adults With Mild-Moderate and High Myopia.

Transl Vis Sci Technol 2022 Jun;11(6):13

Tianjin Medical University Eye Hospital, College of Optometry, Institute of Ophthalmology, National Clinical Medical Research Center for Eye, Ear, Nose and Throat Diseases, Tianjin Branch, Tianjin Key Laboratory of Retinal Function and Diseases, Tianjin, China.

Purpose: The purpose of this study was to explore the characteristics of pupil offset in young Asian adults with myopia.

Methods: In total, 1200 eyes (600 young adults, 18-35 years old) were divided into mild-moderate and high groups according to equivalent spherical diopters (SEQ). The pupil offset and its X and Y components were compared between the groups. Linear correlation was analyzed among pupil offset, X and Y components, and SEQ. Multiple linear regression analysis was conducted for pupil offset and eye parameters.

Results: The mean age of all subjects was 22.5 ± 4.8 years. The mean magnitude of the pupil offset (0.18 ± 0.09 mm vs. 0.15 ± 0.08 mm) and Y component (0.12 ± 0.08 mm vs. 0.10 ± 0.07 mm) were larger in the high group than in the mild-moderate group (P < 0.05). The magnitude of pupil offset, X and Y components, and SEQ were positively correlated. The pupil center (PC) of the right eye in the mild-moderate group was mainly superotemporal to the corneal vertex and mainly superonasal for the left eye and both eyes in the high group. Multiple linear regression analysis revealed that the magnitude of pupil offset correlated with central corneal thickness, intraocular pressure, and mean corneal curvature (P < 0.05).

Conclusions: The magnitude of the pupil offset that correlated with partial eye parameters and its X and Y components increased as the SEQ increased, and the PC gradually shifted toward the superonasal direction in young Asian adults with myopia.

Translational Relevance: Subjects with high myopia with a larger pupil offset should be considered for better postoperative visual quality during refractive surgery.
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http://dx.doi.org/10.1167/tvst.11.6.13DOI Listing
June 2022

Structure-based optimization of Toddacoumalone as highly potent and selective PDE4 inhibitors with anti-inflammatory effects.

Biochem Pharmacol 2022 Jun 8;202:115123. Epub 2022 Jun 8.

National-Local Joint Engineering Laboratory of Druggability and New Drugs Evaluation, Guangdong Province Engineering Laboratory for Druggability and New Drug Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, 510006 Guangzhou, PR China. Electronic address:

Phosphodiesterase-4 (PDE4) is an important drug target for inflammatory diseases. Previously, we identified a series of novel PDE4 inhibitors derived from the natural Toddacoumalone, among which the hit compound 2 with a naphthyridine scaffold showed moderate potency with the IC value of 400 nM. Based on the co-crystal structure of PDE4D-2, further structural optimizations and structure-activity relationship studies led to a highly potent PDE4 inhibitor 23a with the IC value of 0.25 nM and excellent selectivity profiles over other PDEs (>4000-fold). The co-crystal structure of PDE4D-23a elucidated that 23a has strong interactions with the M and Q pocket of PDE4D. Importantly, compound 23a significantly inhibits the release of inflammatory cytokines TNF-α and IL-6 in lipopolysaccharide-stimulated RAW264.7 cells. Thus, compound 23a with a naphthyridine scaffold is a promising PDE4 inhibitor for the treatment of inflammatory diseases.
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http://dx.doi.org/10.1016/j.bcp.2022.115123DOI Listing
June 2022

Cerebral cavernous malformation development in chronic mouse models driven by dual recombinases induced gene deletion in brain endothelial cells.

J Cereb Blood Flow Metab 2022 Jun 10:271678X221105995. Epub 2022 Jun 10.

Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.

Cerebral cavernous malformation (CCM) is a brain vascular disease which can cause stroke, cerebral hemorrhage and neurological deficits in affected individuals. Loss-of-function mutations in three genes (, and ) cause CCM disease. Multiple mouse models for CCM disease have been developed although each of them are associated with various limitations. Here, we employed the Dre-Cre dual recombinase system to specifically delete genes in brain endothelial cells. In this new series of CCM mouse models, robust CCM lesions now develop in the cerebrum. The survival curve and lesion burden analysis revealed that deletion causes modest CCM lesions with a median life expectance of ∼10 months and gene deletion leads to the most severe CCM lesions with median life expectance of ∼2 months. The extended lifespan of these mutant mice enables their utility in behavioral analyses of neurologic deficits in adult mice, and allow the development of methods to quantify lesion burden in mice over time and also permit longitudinal drug testing in live animals.
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http://dx.doi.org/10.1177/0271678X221105995DOI Listing
June 2022

Discovery of Dipyridamole Analogues with Enhanced Metabolic Stability for the Treatment of Idiopathic Pulmonary Fibrosis.

Molecules 2022 May 26;27(11). Epub 2022 May 26.

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.

Dipyridamole, apart from its well-known antiplatelet and phosphodiesterase inhibitory activities, is a promising old drug for the treatment of pulmonary fibrosis. However, dipyridamole shows poor pharmacokinetic properties with a half-life (T) of 7 min in rat liver microsomes (RLM). To improve the metabolic stability of dipyridamole, a series of pyrimidopyrimidine derivatives have been designed with the assistance of molecular docking. Among all the twenty-four synthesized compounds, compound showed outstanding metabolic stability (T = 67 min) in RLM, with an IC of 332 nM against PDE5. Furthermore, some interesting structure-activity relationships (SAR) were explained with the assistance of molecular docking.
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http://dx.doi.org/10.3390/molecules27113452DOI Listing
May 2022

Ursolic Acid Protects Neurons in Temporal Lobe Epilepsy and Cognitive Impairment by Repressing Inflammation and Oxidation.

Front Pharmacol 2022 16;13:877898. Epub 2022 May 16.

Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, China.

Temporal lobe epilepsy (TLE) is characterized as an impaired ability of learning and memory with periodic and unpredictable seizures. Status epilepticus (SE) is one of the main causes of TLE. Neuroinflammation and oxidative stress are directly involved in epileptogenesis and neurodegeneration, promoting chronic epilepsy and cognitive deficit. Previous studies have shown that ursolic acid (UA) represses inflammation and oxidative stress, contributing to neuroprotection. Herein, we demonstrated that UA treatment alleviated seizure behavior and cognitive impairment induced by epilepsy. Moreover, UA treatment rescued hippocampal neuronal damage, aberrant neurogenesis, and ectopic migration, which are commonly accompanied by epilepsy occurrence. Our study also demonstrated that UA treatment remarkably suppressed the SE-induced neuroinflammation, evidenced by activated microglial cells and decreased inflammation factors, including TNF-α and IL-1β. Likewise, the expression levels of oxidative stress damage markers and oxidative phosphorylation (OXPHOS) enzyme complexes of mitochondria were also remarkably downregulated following the UA treatment, suggesting that UA suppressed the damage caused by the high oxidative stress and the defect mitochondrial function induced by SE. Furthermore, UA treatment attenuated GABAergic interneuron loss. In summary, our study clarified the notable anti-seizure and neuroprotective properties of UA in pilocarpine-induced epileptic rats, which is mainly achieved by abilities of anti-inflammation and anti-oxidation. Our study indicates the potential advantage of UA application in ameliorating epileptic sequelae.
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http://dx.doi.org/10.3389/fphar.2022.877898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169096PMC
May 2022

Integrative epigenomic and transcriptomic analysis reveals the requirement of JUNB for hematopoietic fate induction.

Nat Commun 2022 Jun 6;13(1):3131. Epub 2022 Jun 6.

Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing, 100084, China.

Human pluripotent stem cell differentiation towards hematopoietic progenitor cell can serve as an in vitro model for human embryonic hematopoiesis, but the dynamic change of epigenome and transcriptome remains elusive. Here, we systematically profile the chromatin accessibility, H3K4me3 and H3K27me3 modifications, and the transcriptome of intermediate progenitors during hematopoietic progenitor cell differentiation in vitro. The integrative analyses reveal sequential opening-up of regions for the binding of hematopoietic transcription factors and stepwise epigenetic reprogramming of bivalent genes. Single-cell analysis of cells undergoing the endothelial-to-hematopoietic transition and comparison with in vivo hemogenic endothelial cells reveal important features of in vitro and in vivo hematopoiesis. We find that JUNB is an essential regulator for hemogenic endothelium specialization and endothelial-to-hematopoietic transition. These studies depict an epigenomic roadmap from human pluripotent stem cells to hematopoietic progenitor cells, which may pave the way to generate hematopoietic progenitor cells with improved developmental potentials.
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http://dx.doi.org/10.1038/s41467-022-30789-4DOI Listing
June 2022

Predictive value of next-generation sequencing-based minimal residual disease after CAR-T cell therapy.

Bone Marrow Transplant 2022 Jun 1. Epub 2022 Jun 1.

Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

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http://dx.doi.org/10.1038/s41409-022-01699-2DOI Listing
June 2022

Relation Matters: Foreground-aware Graph-based Relational Reasoning for Domain Adaptive Object Detection.

IEEE Trans Pattern Anal Mach Intell 2022 Jun 1;PP. Epub 2022 Jun 1.

Domain Adaptive Object Detection (DAOD) focuses on improving the generalization ability of object detectors via knowledge transfer. Recent advances in Domain Adaptive Object Detection (DAOD) change the emphasis of theadaptation process from global to local in virtue of fine-grained feature alignment methods. However, both the global and local alignment approaches fail to capture the topological relations among different foreground objects as the explicit dependencies and interactions between and within domains are neglected. In this case, only seeking one-vs-one alignment does not necessarily ensure the precise knowledge transfer. Moreover, conventional alignment-based approaches may be vulnerable to catastrophic overfitting regarding those less transferable regions (e.g. backgrounds) due to the accumulation of inaccurate localization results in the target domain. To remedy these issues, we first formulate DAOD as an open-set domain adaptation problem, in which the foregrounds and backgrounds are seen as the "known classes" and "unknown class" respectively. Accordingly, we propose a new and general framework for DAOD, named Foreground-aware Graph-based Relational Reasoning (FGRR), which incorporates graph structures into the detection pipeline to explicitly model the intra- and inter-domain foreground object relations on both pixel and semantic spaces, thereby endowing the DAOD model with the capability of relational reasoning beyond the popular alignment-based paradigm. FGRR first identifies the foreground pixels and regions by searching reliable correspondence and cross-domain similarity regularization respectively. Theinter-domain visual and semantic correlations are hierarchically modeled via bipartite graph structures, and theintra-domain relations are encoded via graph attention mechanisms. Through message-passing, each node aggregates semantic and contextual information from the same and opposite domain to substantially enhance its expressive power. Empirical results demonstrate that the proposed FGRR exceeds the state-of-the-art performance on four DAOD benchmarks.
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http://dx.doi.org/10.1109/TPAMI.2022.3179445DOI Listing
June 2022

Changes in asphericity of anterior and posterior corneal surfaces for mild-moderate and high myopia after topography-guided FS-LASIK.

Int Ophthalmol 2022 May 30. Epub 2022 May 30.

Tianjin Medical University Eye Hospital, College of Optometry, Institute of Ophthalmology, National Clinical Medical Research Center for Eye, Ear, Nose and Throat Diseases, Tianjin Branch, Tianjin Key Laboratory of Retinal Function and Diseases, Tianjin, 300384, China.

Purpose: To compare changes in asphericity of anterior and posterior corneal surfaces for different myopia patients after corneal topography-guided femtosecond-assisted laser in situ keratomileuses (FS-LASIK), and to analyze correlations between asphericity of corneal surfaces and preoperative spherical equivalence (SEQ).

Methods: In this prospective study, 59 patients who underwent corneal topography-guided FS-LASIK surgery were enrolled and divided into the mild-moderate myopia group (67 eyes) and the high myopia group (44 eyes). Postoperative follow-ups were performed at 1, 3, and 6 months. Postoperative changes in aspherical coefficient (Q values), corneal higher-order aberrations (HOAs), and spherical aberrations (Z) were compared between the two groups. Relevance between Q value changes and SEQ, HOAs, and Z as well as between SEQ and changes of HOAs and Z was analyzed.

Results: There was a significant increase in Q values of the anterior (each diameter) and posterior (6-8 mm) corneal surface in both groups than before surgery (P < 0.001). Q values of corneal anterior (each diameter) and posterior (7-9 mm) surface in the high group were considerably larger than the mild-moderate group (P < 0.05). Corneal anterior surface HOAs and Z values in the high group largely exceeded those of the mild-moderate group (P < 0.001). The preoperative SEQ was linearly correlated with postoperative anterior Q change (ΔQ), HOAs change (ΔHOAs), and spherical aberration change (ΔZ).

Conclusion: The changes of corneal asphericity in patients with high myopia were greater than mild-moderate myopia, with more corneal HOAs and Z introduced when corneal topography-guided FS-LASIK was conducted.
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http://dx.doi.org/10.1007/s10792-022-02356-9DOI Listing
May 2022

Evaluation of coating uniformity for the digestion-aid tablets by portable near-infrared spectroscopy.

Int J Pharm 2022 Jun 23;622:121833. Epub 2022 May 23.

Technology and Innovation Center of Jiangxi Traditional Chinese Medicine Manufacturing and Process Quality Control, Nanchang, Jiangxi 330004, PR China; College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China. Electronic address:

Process analysis can effectively stabilize pharmaceutical quality and optimize the control of production process. For the sustained-release digestion-aid tablets, the coating film thickness is an important indicator to measure the quality of products. Traditional method mainly spot-checks tablets and measures with visual microscopy, which is time-consuming and laborious. This study attempted to use a portable near-infrared spectroscopy for rapid detection of a Chinese medicine tablets from production line. First, PLS regression models were established for coating film at twelve different locations of the tablet section, and the results showed that the correlation coefficients of training and validation sets were all over 0.80. Subsequently, the twelve locations were divided into six groups to further establish regressions. After chemometrics optimization, the optimal of six group models were generally better than single location models, with R and R all above 0.85, and RMSEV values all below 2.0. The mean relative error of prediction of the optimal model was 9.49%. The pharmaceutical process detection based on the portable NIR spectroscopy met the demand of managing digestion-aid tablet coating data conveniently. The proposed approach can successfully realize on-site and online pharmaceutical monitoring and has a promising practical value.
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http://dx.doi.org/10.1016/j.ijpharm.2022.121833DOI Listing
June 2022

Fabrication of a nanocomposite film decorated with highly dispersive nanoparticles by following an interface-induced strategy.

Chem Commun (Camb) 2022 Jun 9;58(47):6753-6756. Epub 2022 Jun 9.

Department of Materials Science and Engineering, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, 315211, China.

A polymer nanocomposite film decorated with highly dispersive nanoparticles was prepared by a liquid-liquid interface induced self-assembly method based on a breath figure process. The distribution as well as the orientation preference of the Janus particles within the polymer matrix could be dynamically controlled by adjusting the environmental conditions. Antibacterial and photocatalytic functionality was obtained for the nanocomposite films decorated with silver and titanium dioxide nanoparticles, respectively.
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http://dx.doi.org/10.1039/d2cc01871cDOI Listing
June 2022

A NIR-II emissive polymer AIEgen for imaging-guided photothermal elimination of bacterial infection.

Biomaterials 2022 Jul 16;286:121579. Epub 2022 May 16.

MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China. Electronic address:

The development of antibiotics resistance has made multidrug-resistant (MDR) bacterial infection one of the most serious global health issues. Photothermal therapy (PTT) is an emerging therapeutic mode which can be applied to bacterial infection without inducing resistance. Moreover, enhanced therapeutic efficacy and less tissue damage can be realized with NIR-II fluorescence imaging (FLI) guided PTT. Herein, a polymeric luminogen with aggregation-induced emission (AIEgens) characteristics, poly(dithieno[3,2-b:2',3'-d]pyrrole-benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole)) (PDTPTBT), was synthesized and used as a photothermal agent for PTT of bacterial infections. PDTPTBT was encapsulated into liposomes (L-PDTPTBT) for improved water dispersibility. Upon 808 nm NIR irradiation, L-PDTPTBT can eliminate multiple bacteria including the Gram-positive methicillin-resistant Staphylococcus aureus and Enterococcus faecalis, the Gram-negative Escherichia coli and Pseudomonas aeruginosa. Serious damage of bacterial membrane and leakage of cytoplasm is observed after photothermal treatment using L-PDTPTBT. The potential of the formulation has been demonstrated in two infected animal models: (i) a subcutaneous abscess model and (ii) a diabetic skin infection model. In the diabetic skin infection model, the death of mice is largely suppressed and the wounds can heal more quickly with treatment of L-PDTPTBT under NIR irradiation. The excellent photothermal bactericidal ability and low cytotoxicity make L-PDTPTBT potential candidate for treating MDR bacterial infections in the future.
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http://dx.doi.org/10.1016/j.biomaterials.2022.121579DOI Listing
July 2022

Associations of Plasma Fatty Acid Patterns During Pregnancy With Gestational Diabetes Mellitus.

Front Nutr 2022 6;9:836115. Epub 2022 May 6.

Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Limited studies have explored the difference of fatty acid profile between women with and without gestational diabetes mellitus (GDM), and the results were inconsistent. Individual fatty acids tend to be interrelated because of the shared food sources and metabolic pathways. Thus, whether fatty acid patters during pregnancy were related to GDM odds needs further exploration.

Objective: To identify plasma fatty acid patters during pregnancy and their associations with odds of GDM.

Methods: A hospital-based case-control study including 217 GDM cases and 217 matched controls was carried out in urban Wuhan, China from August 2012 to April 2015. All the participants were enrolled at the time of GDM screening and provided fasting blood samples with informed consent. We measured plasma concentrations of fatty acids by gas chromatography-mass spectrometry, and derived potential fatty acid patterns (FAPs) through principal components analysis. Conditional logistic regression and restricted cubic spline model were used to evaluate the associations between individual fatty acids or FAPs and odds of GDM.

Results: Twenty individual fatty acids with relative concentrations ≥0.05% were included in the analyses. Compared with control group, GDM group had significantly higher concentrations of total fatty acids, 24:1n-9, and relatively lower levels of 14:0, 15:0, 17:0, 18:0, 24:0, 16:1n-7, 20:1n-9,18:3n-6, 20:2n-6, 18:3n-3, 20:3n-3, 22:5n-3. Two novel patterns of fatty acids were identified to be associated with lower odds of GDM: (1) relatively higher odd-chain fatty acids, 14:0, 18:0, 18:3n-3, 20:2n-6, 20:3n-6 and lower 24:1n-9 and 18:2n-6 [adjusted odds ratio (OR) (95% confidence interval) (CI) for quartiles 4 vs. 1: 0.42 (0.23-0.76), -trend = 0.002], (2) relatively higher n-3 polyunsaturated fatty acids, 24:0, 18:3n-6 and lower 16:0 and 20:4n-6 [adjusted OR (95% CI) for quartiles 4 vs. 1: 0.48 (0.26-0.90), -trend = 0.018].

Conclusion: Our findings suggested that two novel FAPs were inversely associated with GDM odds. The combination of circulating fatty acids could be a more significant marker of GDM development than individual fatty acids or their subgroups.
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http://dx.doi.org/10.3389/fnut.2022.836115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121815PMC
May 2022

TRPC5OS induces tumorigenesis by increasing ENO1-mediated glucose uptake in breast cancer.

Transl Oncol 2022 Aug 16;22:101447. Epub 2022 May 16.

Department of Breast Surgery, The First Hospital Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China. Electronic address:

Breast cancer is the most common malignant tumor worldwide and the leading cause of cancer-related deaths in female. Metabolic reprogramming plays critical roles in breast tumorigenesis and induces enhanced glucose uptake and glycolysis. TRPC5OS is encoded by short transient receptor potential channel 5 opposite strand, and predicted to correlate with tumor metabolic reprogramming. Here we aim to elucidate the function of TRPC5OS in aberrant metabolism mediated tumorigenesis. We detected TRPC5OS expression levels in cell lines and tissues by quantitative real-time polymerase chain reaction and immunohistochemistry. Then we assessed the effects of TRPC5OS on proliferation and cell cycle progression in breast cancer cells by cell counting kit-8, colony-formation, EdU-incorporation assays and flow cytometry. Tumor growth in vivo was observed in a mouse xenograft model. Mass spectrum analyses were performed to identify potential interactors of TRPC5OS in tumor cells, and the interaction between TRPC5OS and interactors was validated by co-immunoprecipitation (CO-IP), western blots, and immunofluorescent staining. Glucose uptake was measured by liquid scintillation spectrometry. TRPC5OS highly expresses both in breast tumors and cell lines, and might be an independent prognostic marker for breast cancer patients. Overexpressed TRPC5OS promotes breast cancer cell proliferation, cell cycle progression, and enhances tumor xenograft growth. Mass spectral and CO-IP data showed that TRPC5OS interacts with ENO1. We also demonstrate that TRPC5OS could enhance ENO1/PI3K/Akt-mediated glucose uptake in breast cancer cells. Our study demonstrated that TRPC5OS promotes breast tumorigenesis by ENO1/PI3K/Akt-mediated glucose uptake. TRPC5OS might be an independent prognostic marker and potential therapeutic target for breast cancer patients.
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http://dx.doi.org/10.1016/j.tranon.2022.101447DOI Listing
August 2022

Piperazine-Based Mitochondria-Immobilized pH Fluorescent Probe for Imaging Endogenous ONOO and Real-Time Tracking of Mitophagy.

ACS Appl Bio Mater 2022 Jun 15;5(6):2777-2785. Epub 2022 May 15.

Institute of Environmental Science, Shanxi University, Taiyuan 030006, P. R. China.

ONOO is mainly produced in mitochondria, and dysfunctional and damaged mitochondria are degraded in lysosomes through autophagy, so it is important to synthesize a single probe for dual detection of ONOO and mitophagy. Unfortunately, mitochondria-immobilized fluorescent probes for dual detection of ONOO and mitophagy have not yet been developed. Hence, we first reported a piperazine-based mitochondria-immobilized red-emitting fluorescent probe (PMR), which not only can detect ONOO but also could be used to image cellular mitophagy by the pH variations because of the protonation of the piperazine moiety. PMR was designed and prepared by introducing a piperazine ring as the pH response group, a lipophilic cation as the targeting mitochondria moiety, and benzyl chloride for immobilizing mitochondrial proteins through thiol groups. PMR displayed an enhanced fluorescence response at 640 nm through mitochondrial acidification. Using these advantages of PMR, which was successfully used for visualizing the mitophagy process induced by rapamycin or starvation, and chloroquine can inhibit rapamycin-induced mitophagy and prevent the fusion of autophagosomes and lysosomes. PMR also showed good sensitivity with a detection limit of 23 nM to ONOO, which was successfully applied in imaging exogenous/endogenous ONOO. Combining the above design, PMR may be used to study the detailed function of the mitophagy and ONOO-associated physiological and pathological processes.
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http://dx.doi.org/10.1021/acsabm.2c00213DOI Listing
June 2022

Design and Evaluation of In-Plane Silicon Microneedles Fabricated with Post-CMOS Compatible Processes.

Sens Actuators A Phys 2022 Apr 29;336. Epub 2022 Jan 29.

Micro/Nanoelectronics and Energy Laboratory, School of Engineering and Computer Science, Washington State University, Vancouver, WA 98686, United States.

In this paper, a comprehensive study was carried out on in-plane silicon (Si) microneedles, a useful tool for transdermal drug delivery and sample collection. Microneedles with eleven designs were investigated by post-complementary metal-oxide-semiconductor (CMOS) compatible microfabrication processes and characterized via pricking tests by insertion in chicken breast flesh. Mechanical strength of all designs were also evaluated by theoretical calculation and finite element modeling (FEM) for bending and buckling analysis. To efficiently improve the sharpness and insertion, the wedge-shaped needle tips with thickness determined by Si wafer thickness were sharpened by a wet chemical etching process. Insertion forces recorded from pricking tests and bending and buckling from theoretical calculation and FEM analysis before and after etching were compared. The results showed that the insertion force, free bending force and the maximum buckling force were all reduced and the maximum bending stress were improved after tip sharpening. Furthermore, the buckling safety factor of all eleven designs was great than 1 and the maximum bending stress was less than the fracture strength of Si, indicating that our in-plane Si microneedles are robust enough for insertion into human skin.
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http://dx.doi.org/10.1016/j.sna.2022.113407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104144PMC
April 2022

Characteristics of acute kidney injury and its impact on outcome in patients with acute-on-chronic liver failure.

BMC Gastroenterol 2022 May 11;22(1):231. Epub 2022 May 11.

Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, Tianjin, 300170, China.

Objective: Acute kidney injury (AKI) is a common and life-threatening complication of liver failure. The purpose of this study is to construct a nomogram and online calculator to predict the development of hospital-acquired acute kidney injury (HA-AKI) in patients with acute-on-chronic liver failure (ACLF), which may contribute to the prognosis of ACLF.

Methods: 574 ACLF patients were evaluated retrospectively. AKI was defined by criteria proposed by International Club of Ascites (ICA) and divided into community-acquired and hospital-acquired AKI (CA-AKI and HA-AKI). The difference between CA-AKI and HA-AKI, factors associated with development into and recovered from AKI periods. The risk factors were identified and nomograms were developed to predict the morbidity of HA-AKI in patients with ACLF.

Results: Among 574 patients, 217(37.8%) patients had AKI, CA-AKI and HA-AKI were 56 (25.8%) and 161 (74.2%) respectively. The multivariate logistic regression model (KP-AKI) for predicting the occurrence of HA-AKI were age, gastrointestinal bleeding, bacterial infections, albumin, total bilirubin, blood urea nitrogen and prothrombin time. The AUROC of the KP-AKI in internal and external validations were 0.747 and 0.759, respectively. Among 217 AKI patients, 81(37.3%), 96(44.2%) and 40(18.4%) patients were with ICA-AKI stage progression, regression and fluctuated in-situ, respectively. The 90-day mortality of patients with AKI was 55.3% higher than non-AKI patients 21.6%. The 90-day mortality of patients with progression of AKI was 88.9%, followed by patients with fluctuated in-situ 40% and regression of AKI 33.3%.

Conclusions: The nomogram constructed by KP-AKI can be conveniently and accurately in predicting the development of HA-AKI, and AKI can increase the 90-day mortality significantly in ACLF patients. Trial registration Chinese clinical trials registry: ChiCTR1900021539.
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http://dx.doi.org/10.1186/s12876-022-02316-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9092688PMC
May 2022

Free energy perturbation (FEP)-guided scaffold hopping.

Acta Pharm Sin B 2022 Mar 30;12(3):1351-1362. Epub 2021 Sep 30.

School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China.

Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies Δ between ligands and their target, which were more consistent with the experimental binding potencies Δ (the mean absolute deviations  < 2 kcal/mol) than those Δ or Δ predicted by the MM-PBSA or MM-GBSA method. Lead had an IC of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.
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http://dx.doi.org/10.1016/j.apsb.2021.09.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9072250PMC
March 2022

Auditory and Speech Outcomes of Cochlear Implantation in Children With Auditory Neuropathy Spectrum Disorder: A Systematic Review and Meta-Analysis.

Ann Otol Rhinol Laryngol 2022 May 2:34894221092201. Epub 2022 May 2.

Department of Otolaryngology-Head and Neck Surgery, Children's Hospital of Fudan University, Shanghai, China.

Objective: The aim of this meta-analysis was to critically assess the effect of cochlear implantation on auditory and speech performance outcomes of children with auditory neuropathy spectrum disorder (ANSD).

Material And Methods: A systematic literature search was conducted on PubMed, EMbase, and Web of Science. The outcomes included speech recognition score, Categories of Auditory Performance (CAP), Speech Intelligibility Rating (SIR) score, and open-set speech perception. Results were expressed as standardized mean difference (SMD) or risk ratio (RR) with a 95% confidence interval (95% CI).

Results: A total of 15 studies was included in this meta-analysis. Pooled data showed that, there were no significant differences between ANSD and sensorineural hearing loss (SNHL) groups in terms of speech recognition score (SMD = 0.01, 95% CI: -0.45, 0.47;  = .959),CAP (SMD = 0.71, 95% CI: -0.13, 1.54;  = .098), SIR score (SMD = -0.09, 95% CI: -0.49, 0.32;  = .667), and open-set speech perception (RR = 0.85, 95% CI: 0.69, 1.05;  = .142). Sensitivity analysis by removing individual studies one at a time showed that the overall estimate and level of heterogeneity did not change substantially.

Conclusion: The current evidence suggested that children with ANSD who underwent cochlear implants achieved comparable effects in auditory and speech performance as children with non-ANSD SNHL.
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http://dx.doi.org/10.1177/00034894221092201DOI Listing
May 2022

The C-Terminal Transmembrane Domain of Cowpea Mild Mottle Virus TGBp2 Is Critical for Plasmodesmata Localization and for Its Interaction With TGBp1 and TGBp3.

Front Microbiol 2022 15;13:860695. Epub 2022 Apr 15.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Key Laboratory of Biotechnology in Plant Protection of MOA of China and Zhejiang Province, Institute of Plant Virology, Ningbo University, Ningbo, China.

The movement of some plant RNA viruses is mediated by triple gene block (TGB) proteins, which cooperate to transfer the viral genome from cell to cell through plasmodesmata. Here, we investigated the function of the TGB proteins of cowpea mild mottle virus (CPMMV; genus , family ), which causes severe damage to soybean production. Subcellular localization experiments demonstrated that TGBp1 and TGBp3 were localized to the endoplasmic reticulum (ER), plasmodesmata (PD) and nucleus in leaves. TGBp2 was unusually localized to PD. In protein interaction assays TGBp2 significantly enhanced the interaction between TGBp3 and TGBp1. Interaction assays using deletion mutants showed that the C-terminal transmembrane (TM) domain of TGBp2 is critical for its localization to PD and for its interaction with TGBp1 and TGBp3.
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http://dx.doi.org/10.3389/fmicb.2022.860695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9051516PMC
April 2022

Discovery of catalytic-site-fluorescent probes for tracing phosphodiesterase 5 in living cells.

RSC Adv 2021 Sep 4;11(51):31967-31971. Epub 2021 Oct 4.

School of Pharmaceutical Sciences, Sun Yat-Sen University Guangzhou 510006 China

Small molecule fluorescent probes provide a powerful labelling technology to enhance our understanding of particular proteins. However, the discovery of a proper fluorescent probe for detecting PDE5 is still a challenge due to the highly conservative structure of the catalytic domain in the phosphodiesterase (PDE) families. Herein, we identified probes based on the key amino residues in the ligand binding pocket of PDE5 and catalytic-site-fluorescent probes PCO2001-PCO2003 were well designed and synthesized. Among them, PCO2003 exhibited extraordinary fluorescence properties and the ability to be applied to PDE5 visualization in live cells as well as in pulmonary tissue slices, demonstrating the location and expression level of PDE5 proteins. Overall, the environment-sensitive "turn-on" probe is economical, convenient and rapid for PDE5 imaging, implying that the catalytic-site-fluorescent probe will have a variety of future applications in pathological diagnosis as well as drug screening.
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http://dx.doi.org/10.1039/d1ra06247fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9041563PMC
September 2021

Inhibition of miRNA-1-Mediated Inflammation and Autophagy by Astragaloside IV Improves Lipopolysaccharide-Induced Cardiac Dysfunction in Rats.

J Inflamm Res 2022 23;15:2617-2629. Epub 2022 Apr 23.

Department of Cardiovascular Disease and Key Laboratory of Digestive System Tumor of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu Province, People's Republic of China.

Introduction: Astragaloside IV (AS-IV) is one of the main active components isolated from the traditional Chinese medicinal herb, . The present study was designed to investigate whether the regulation of microRNA-1 (miR-1)-mediated inflammation and autophagy contributes to the protective effect of AS-IV against cardiac dysfunction in rats treated with lipopolysaccharides (LPS).

Methods: Animal model of cardiac dysfunction in rats or cellular model of injured H9c2 heart cell line was established by using LPS. Echocardiography, electron microscopy, enzyme-linked immunosorbent assay, immunofluorescence, quantitative RT-PCR, and Western blotting were used to determine the cardiac function and expression of inflammation- and autophagy-related proteins at both the mRNA and protein levels.

Results: LPS caused cardiac dysfunction in rats or injury in H9c2 cells and induced inflammation and autophagy. Compared with LPS treatment, AS-IV treatment attenuated cardiac dysfunction or cell injury, accompanied by inhibition of inflammation and autophagy. However, the miR-1 mimics partly abolished the effects of AS-IV. In addition, the effect of the miR-1 inhibitor was similar to that of AS-IV in the LPS model. Further analyses showed that AS-IV treatment decreased the mRNA expression of miR-1 in the heart tissue of rats and H9c2 cells treated with LPS.

Conclusion: These results suggest that AS-IV attenuated cardiac dysfunction caused by LPS by inhibiting miR-1-mediated inflammation and autophagy, thereby providing a novel mechanism for the protection against cardiac diseases.
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http://dx.doi.org/10.2147/JIR.S362368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045596PMC
April 2022

Imaging and audiological features of children with cochlear nerve deficiency.

Ear Nose Throat J 2022 May 1:1455613221096622. Epub 2022 May 1.

Department of Neurology, Children's hospital of Fudan University, Shanghai, China.

Cochlear nerve deficiency (CND) accounts for 10-19% of hearing loss in children; this study investigated the imaging and audiological features of 25 CND children. A total of 563 children with an unpassed automatic auditory brainstem response were diagnosed with hearing loss in our department between December 2018 and December 2021, of which, the imaging and audiological features of 25 children (25/563, 4.4%) diagnosed with a CND were reviewed. Twenty-one (21/25, 84.0%) CND children had unilateral deafness, and 4 cases of bilateral deafness. All deaf ears were diagnosed as severe hearing loss due to an auditory brainstem response. CM waves were recorded in 8 cases and DPOAE in 3 cases, suggesting the audiological characteristics of auditory neuropathy spectrum disorders (ANSD). MRI results indicated 23 cases had small cochlear nerves and 2 cases had absent cochlear nerves. No genetic mutations were identified in the 25 CND children. Most CND children had unilateral hearing loss; therefore, high-resolution MRI imaging of the internal auditory canal should be performed to detect the auditory nerve in children with severe hearing loss. Some CND children had characteristics of ANSD.
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http://dx.doi.org/10.1177/01455613221096622DOI Listing
May 2022

Associations of urinary perchlorate, nitrate and thiocyanate with central sensitivity to thyroid hormones: A US population-based cross-sectional study.

Environ Int 2022 06 20;164:107249. Epub 2022 Apr 20.

Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: Perchlorate, nitrate, and thiocyanate are three well-known sodium iodine symporter inhibitors, however, associations of their individual and concurrent exposure with central thyroid hormones sensitivity remain unclear.

Objectives: To investigate the associations of urinary perchlorate, nitrate, thiocyanate, and their co-occurrence with central thyroid hormones sensitivity among US general adults.

Methods: A total of 7598 non-pregnant adults (weighted mean age 45.9 years and 52.9% men) from National Health and Nutritional Examination Survey 2007-2012 were included in this cross-sectional study. Central sensitivity to thyroid hormones was estimated with the Parametric Thyroid Feedback Quantile-based Index (PTFQI). Ordinary least-squares regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models were performed to examine the associations of three anions and their co-occurrence with PTFQI.

Results: The weighted mean values of urinary perchlorate, nitrate, thiocyanate, and perchlorate equivalent concentration (PEC) were 5.48 μg/L, 57.59 mg/L, 2.65 mg/L, and 539.8 μg/L, respectively. Compared with the lowest quartile, the least-square means difference (LSMD) of PTFQI was -0.0516 (LSMD ± SE: -0.0516 ± 0.0185, P < 0.01) in the highest perchlorate quartile. On average, PTFQI decreased by 0.0793 (LSMD ± SE: -0.0793 ± 0.0205, P < 0.001) between the highest and lowest thiocyanate quartile. Compared with those in the lowest quartile, participants in the highest PEC quartile had significantly decreased PTFQI levels (LSMD ± SE: -0.0862 ± 0.0188, P < 0.001). The WQS of three goitrogens, was inversely associated with PTFQI (β: -0.051, 95% CI: -0.068, -0.034). In BKMR model, PTFQI significantly decreased when the levels of three anions were at or above their 60th percentiles compared to the median values.

Conclusions: Higher levels of urinary perchlorate, thiocyanate, and co-occurrence of three goitrogens were associated with increased central thyroid hormones sensitivity among US general adults. Further studies are warranted to replicate our results and elucidate the underlying causative mechanistic links.
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http://dx.doi.org/10.1016/j.envint.2022.107249DOI Listing
June 2022

The function of nuclear hormone receptor 4A signaling in the human reproductive system: A review.

J Obstet Gynaecol Res 2022 Apr 20. Epub 2022 Apr 20.

Department of Gynecology and Obstetrics, The Fourth Affiliated Hospital of Anhui Medical, Anhui, China.

Aim: This review aims to summarize the research focused upon the functions of nuclear hormone receptor 4A (NR4A) in the human reproductive system. The research questions addressed are to decipher what role the NR4A subfamily plays in the regulation of the human reproductive system and effects upon fertility issues through regulation of the expression of the NR4A subfamily.

Methods: The electronic database PubMed was searched for studies published before November 2021. Keywords included "NR4A," "trophoblast," "decidualization," "folliculogenesis," "estrogen," "pregnancy," "Leydig cells," "fertility," and "reproductive." Relevant references from retrieved manuscripts and review articles were also searched manually.

Results: NR4A subfamily are involved in trophoblast differentiation, endometrial decidualization, embryo adhesion, secretion of related hormones, and regulation of spontaneous term labor. Besides, many studies have provided strong evidence that they play critical roles in spermatogenesis. Furthermore, Multiple mechanisms can affect the expression of NR4As. Broadly, NR4A family receptors affect the human reproductive system in multiple ways.

Conclusions: Further research is needed to specifically dissect the functions and regulatory mechanisms of these receptors and their pharmaceutical antagonists and agonists. The connection between the NR4A subfamily and a variety of reproductive disorders needs to be proven experimentally such that further examination of human tissue is required to assess the role of these receptors in human reproductive diseases.
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http://dx.doi.org/10.1111/jog.15264DOI Listing
April 2022
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